Amyloid
A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.
Amyloid beta-Peptides
Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.
Serum Amyloid A Protein
Amyloid beta-Protein Precursor
Islet Amyloid Polypeptide
A pancreatic beta-cell hormone that is co-secreted with INSULIN. It displays an anorectic effect on nutrient metabolism by inhibiting gastric acid secretion, gastric emptying and postprandial GLUCAGON secretion. Islet amyloid polypeptide can fold into AMYLOID FIBRILS that have been found as a major constituent of pancreatic AMYLOID DEPOSITS.
Amyloidosis
A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.
Cerebral Amyloid Angiopathy
A heterogeneous group of sporadic or familial disorders characterized by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES. Clinical features include multiple, small lobar CEREBRAL HEMORRHAGE; cerebral ischemia (BRAIN ISCHEMIA); and CEREBRAL INFARCTION. Cerebral amyloid angiopathy is unrelated to generalized AMYLOIDOSIS. Amyloidogenic peptides in this condition are nearly always the same ones found in ALZHEIMER DISEASE. (from Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed., 2005)
Serum Amyloid P-Component
Amyloid Neuropathies
Disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. Familial, primary (nonfamilial), and secondary forms have been described. Some familial subtypes demonstrate an autosomal dominant pattern of inheritance. Clinical manifestations include sensory loss, mild weakness, autonomic dysfunction, and CARPAL TUNNEL SYNDROME. (Adams et al., Principles of Neurology, 6th ed, p1349)
Amyloid Precursor Protein Secretases
Alzheimer Disease
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)
Congo Red
Amyloid Neuropathies, Familial
Inherited disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. The different clinical types based on symptoms correspond to the presence of a variety of mutations in several different proteins including transthyretin (PREALBUMIN); APOLIPOPROTEIN A-I; and GELSOLIN.
Prealbumin
Peptide Fragments
Aspartic Acid Endopeptidases
Presenilin-1
Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans.
Mice, Transgenic
Brain
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Cerebral Amyloid Angiopathy, Familial
Prions
Small proteinaceous infectious particles which resist inactivation by procedures that modify NUCLEIC ACIDS and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PRPSC PROTEINS) and the cellular isoform PrPC (PRPC PROTEINS). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include CREUTZFELDT-JAKOB SYNDROME; GERSTMANN-STRAUSSLER SYNDROME; and INSOMNIA, FATAL FAMILIAL.
Protein Structure, Secondary
Neurofibrillary Tangles
Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) UBIQUITINS. As one of the hallmarks of ALZHEIMER DISEASE, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease.
Amino Acid Sequence
tau Proteins
Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES).
Molecular Sequence Data
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Protein Multimerization
Microscopy, Electron, Transmission
Microscopy, Atomic Force
A type of scanning probe microscopy in which a probe systematically rides across the surface of a sample being scanned in a raster pattern. The vertical position is recorded as a spring attached to the probe rises and falls in response to peaks and valleys on the surface. These deflections produce a topographic map of the sample.
Protease Nexins
beta 2-Microglobulin
An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.
Neurons
Disease Models, Animal
Endopeptidases
Circular Dichroism
Insulysin
Microscopy, Electron
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
Protein Conformation
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Presenilin-2
Protein Binding
Mutation
Models, Molecular
Protein Structure, Tertiary
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Protein Structure, Quaternary
Peptides
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Hippocampus
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
alpha-Synuclein
Cerebral Cortex
Spectroscopy, Fourier Transform Infrared
Immunohistochemistry
Neurofibrils
Apolipoproteins E
A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.
Gerstmann-Straussler-Scheinker Disease
An autosomal dominant familial prion disease with a wide spectrum of clinical presentations including ATAXIA, spastic paraparesis, extrapyramidal signs, and DEMENTIA. Clinical onset is in the third to sixth decade of life and the mean duration of illness prior to death is five years. Several kindreds with variable clinical and pathologic features have been described. Pathologic features include cerebral prion protein amyloidosis, and spongiform or neurofibrillary degeneration. (From Brain Pathol 1998 Jul;8(3):499-513; Brain Pathol 1995 Jan;5(1):61-75)
Peptide Termination Factors
Apolipoprotein E4
A major and the second most common isoform of apolipoprotein E. In humans, Apo E4 differs from APOLIPOPROTEIN E3 at only one residue 112 (cysteine is replaced by arginine), and exhibits a lower resistance to denaturation and greater propensity to form folded intermediates. Apo E4 is a risk factor for ALZHEIMER DISEASE and CARDIOVASCULAR DISEASES.
Microglia
The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.
Aging
Cells, Cultured
Presenilins
Neurodegenerative Diseases
Receptors, Islet Amyloid Polypeptide
Neprilysin
Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.
Islets of Langerhans
Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.
Protein Processing, Post-Translational
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Protein Denaturation
Positron-Emission Tomography
An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower.
Acute-Phase Reaction
PC12 Cells
Nuclear Magnetic Resonance, Biomolecular
Maze Learning
Enzyme-Linked Immunosorbent Assay
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Solubility
Trifluoroethanol
Prion Diseases
A group of genetic, infectious, or sporadic degenerative human and animal nervous system disorders associated with abnormal PRIONS. These diseases are characterized by conversion of the normal prion protein to an abnormal configuration via a post-translational process. In humans, these conditions generally feature DEMENTIA; ATAXIA; and a fatal outcome. Pathologic features include a spongiform encephalopathy without evidence of inflammation. The older literature occasionally refers to these as unconventional SLOW VIRUS DISEASES. (From Proc Natl Acad Sci USA 1998 Nov 10;95(23):13363-83)
Protein Stability
Coloring Agents
Gliosis
Membrane Proteins
Brain Chemistry
Islet amyloid polypeptide/amylin messenger RNA and protein expression in human insulinomas in relation to amyloid formation. (1/3010)
OBJECTIVE: Islet amyloid polypeptide (IAPP), also named amylin, is the predominant protein component of amyloid deposits in human islet beta cell tumours of the pancreas (insulinomas). IAPP is co-produced with insulin by islet beta cells. We investigated IAPP expression in relation to insulin expression and to amyloid formation in eleven insulinomas. DESIGN AND METHODS: RNA and protein extracts were prepared from the same pieces of tumour tissue, and from specimens of two normal human pancreata. IAPP and insulin mRNA and peptide content were quantified using Northern blot analysis and radioimmunoassay (RIA) respectively. Molecular forms of IAPP immunoreactivity were analysed by reversed-phase high-performance liquid chromatography (HPLC). The presence of islet hormones and of amyloid was assessed by (immuno)histochemical staining of paraffin sections. Plasma levels of IAPP and insulin prior to tumour resection were determined by RIA. RESULTS: IAPP and insulin mRNA and peptide content varied widely between the tumour specimens, and there was considerable intratumour heterogeneity of peptide content. HPLC analysis indicated correct proteolytic processing of the IAPP precursor protein. Amyloid deposits were detected only in the three tumours with the highest IAPP content. In contrast to insulin, plasma levels of IAPP were not elevated in the insulinoma patients. CONCLUSIONS: The spectrum of hormone production by insulinomas cannot be inferred from only a few tissue sections due to intratumour heterogeneity. Expression of the IAPP and insulin genes is not coupled in insulinomas, which produce properly processed mature IAPP. In addition to IAPP overproduction, additional factors such as intracellular accumulation of IAPP are involved in amyloidogenesis in insulinomas. (+info)Prion domain initiation of amyloid formation in vitro from native Ure2p. (2/3010)
The [URE3] non-Mendelian genetic element of Saccharomyces cerevisiae is an infectious protein (prion) form of Ure2p, a regulator of nitrogen catabolism. Here, synthetic Ure2p1-65 were shown to polymerize to form filaments 40 to 45 angstroms in diameter with more than 60 percent beta sheet. Ure2p1-65 specifically induced full-length native Ure2p to copolymerize under conditions where native Ure2p alone did not polymerize. Like Ure2p in extracts of [URE3] strains, these 180- to 220-angstrom-diameter filaments were protease resistant. The Ure2p1-65-Ure2p cofilaments could seed polymerization of native Ure2p to form thicker, less regular filaments. All filaments stained with Congo Red to produce the green birefringence typical of amyloid. This self-propagating amyloid formation can explain the properties of [URE3]. (+info)Interaction of amylin with calcitonin gene-related peptide receptors in the microvasculature of the hamster cheek pouch in vivo. (3/3010)
1. This study used intravital microscopy to investigate the receptors stimulated by amylin which shares around 50% sequence homology with the vasodilator calcitonin gene-related peptide (CGRP) in the hamster cheek pouch microvasculature in vivo. 2. Receptor agonists dilated arterioles (diameters 20-40 microm). The -log of the concentrations (+/- s.e.mean; n = 8) causing 50% increase in arteriole diameter were: human betaCGRP (10.8 +/- 0.3), human alphaCGRP (10.8 +/- 0.4), rat alphaCGRP (10.4 +/- 0.3). Rat amylin and the CGRP2 receptor selective agonist [Cys(ACM2,7]-human alphaCGRP were 100 fold less potent (estimates were 8.5 +/- 0.4 and 8.2 +/- 0.3 respectively). 3. The GCRP1 receptor antagonist, CGRP8-37 (300 nmol kg(-1); i.v.) reversibly inhibited the increase in diameter evoked by human alphaCGRP (0.3 nM) from 178 +/- 22% to 59 +/- 12% (n = 8; P < 0.05) and by rat amylin (100 nM) from 138 +/- 23% to 68 +/- 24% (n = 6; P < 0.05). CGRP8-37 did not inhibit vasodilation evoked by substance P (10 nM; n = 4: P > 0.05). 4. The amylin receptor antagonist, amylin8-37 (300 nmol kg(-1); i.v.) did not significantly inhibit the increase in diameter evoked by human alphaCGRP (0.3 nM) which was 112 +/- 26% in the absence, and 90 +/- 29% in the presence of antagonist (n = 4; P < 0.05); nor that evoked by rat amylin (100 nM) which was 146 +/- 23% in the absence and 144 +/- 32% in the presence of antagonist (n = 4; P > 0.05). 5. The agonist profile for vasodilatation and the inhibition of this dilatation by CGRP8-37, although not the amylin8-37 indicates that amylin causes vasodilatation through interaction with CGRP1 receptors in the hamster cheek pouch. (+info)The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles. (4/3010)
NIDDM is characterized by islet amyloid deposits and decreased beta-cell mass. Islet amyloid is derived from the locally expressed protein islet amyloid polypeptide (IAPP). While it is now widely accepted that abnormal aggregation of IAPP has a role in beta-cell death in NIDDM, the mechanism remains unknown. We hypothesized that small IAPP aggregates, rather than mature large amyloid deposits, are cytotoxic. Consistent with this hypothesis, freshly dissolved human (h)-IAPP was cytotoxic when added to dispersed mouse and human islet cells, provoking the formation of abnormal vesicle-like membrane structures in association with vacuolization and cell death. Human islet cell death occurred by both apoptosis and necrosis, predominantly between 24 and 48 h after exposure to h-IAPP. In contrast, the addition to dispersed islet cells of matured h-IAPP containing large amyloid deposits of organized fibrils was seldom associated with vesicle-like structures or features of cell death, even though the cells were often encased in the larger amyloid deposits. Based on these observations, we hypothesized that h-IAPP cytotoxicity is mediated by membrane damage induced by early h-IAPP aggregates. Consistent with this hypothesis, application of freshly dissolved h-IAPP to voltage-clamped planar bilayer membranes (a cell-free in vitro system) also caused membrane instability manifested as a marked increase in conductance, increased membrane electrical noise, and accelerated membrane breakage, effects that were absent using matured h-IAPP or rat IAPP solutions. Light-scattering techniques showed that membrane toxicity corresponded to h-IAPP aggregates containing approximately 25-6,000 IAPP molecules, an intermediate-sized amyloid particle that we term intermediate-sized toxic amyloid particles (ISTAPs). We conclude that freshly dissolved h-IAPP is cytotoxic and that this cytotoxicity is mediated through an interaction of ISTAPs with cellular membranes. Once ISTAPs mature into amyloid deposits comprising >10(6) molecules, the capacity of h-IAPP to cause membrane instability and islet cell death is significantly reduced or abolished. These data may have implications for the mechanism of cell death in other diseases characterized by local amyloid formation (such as Alzheimer's disease). (+info)Specific gene expression in pancreatic beta-cells: cloning and characterization of differentially expressed genes. (5/3010)
Identification and characterization of genes expressed preferentially in pancreatic beta-cells will clarify the mechanisms involved in the specialized properties of these cells, as well as providing new markers of the development of type 1 diabetes. Despite major efforts, relatively few beta-cell-specific genes have been characterized. We applied representational difference analysis to identify genes expressed selectively in the pancreatic beta-cell line betaTC1 compared with the pancreatic alpha-cell line alphaTC1 and isolated 26 clones expressed at higher levels in the beta-cells than in the alpha-cells. DNA sequencing revealed that 14 corresponded to known genes (that is, present in GenBank). Only four of those genes had been shown previously to be expressed at higher levels in beta-cells (insulin, islet amyloid polypeptide, neuronatin, and protein kinase A regulatory subunit [RIalpha]). The known genes include transcription factors (STAT6) and mediators of signal transduction (guanylate cyclase). The remaining 12 genes are absent from the GenBank database or are present as expressed sequence tag (EST) sequences (4 clones). Some of the genes are expressed in a highly specific pattern-expression in betaTC1 and islet cells and in relatively few of the non-beta-cell types examined; others are expressed in most cell types tested. The identification of these differentially expressed genes may aid in attaining a clearer understanding of the mechanisms involved in beta-cell function and of the possible immunogens involved in development of type 1 diabetes. (+info)Colchicine inhibition of the first phase of amyloid synthesis in experimental animals. (6/3010)
Colchicine was found to inhibit the first phase of casein-induced synthesis of murine amyloid. When mice were treated with colchicine during the first 7 days of an amyloid induction regimen or when colchicine was given to the donor mice in a transfer model, the amyloidogenic stimulus of casein was blocked completely. Amyloid synthesis was however, not interrupted by the administration of colchicine during the last 7 days of the casein regimen nor by colchicine treatment of recipient mice in a transfer model. (+info)Ancestral origins and worldwide distribution of the PRNP 200K mutation causing familial Creutzfeldt-Jakob disease. (7/3010)
Creutzfeldt-Jakob disease (CJD) belongs to a group of prion diseases that may be infectious, sporadic, or hereditary. The 200K point mutation in the PRNP gene is the most frequent cause of hereditary CJD, accounting for >70% of families with CJD worldwide. Prevalence of the 200K variant of familial CJD is especially high in Slovakia, Chile, and Italy, and among populations of Libyan and Tunisian Jews. To study ancestral origins of the 200K mutation-associated chromosomes, we selected microsatellite markers flanking the PRNP gene on chromosome 20p12-pter and an intragenic single-nucleotide polymorphism at the PRNP codon 129. Haplotypes were constructed for 62 CJD families originating from 11 world populations. The results show that Libyan, Tunisian, Italian, Chilean, and Spanish families share a major haplotype, suggesting that the 200K mutation may have originated from a single mutational event, perhaps in Spain, and spread to all these populations with Sephardic migrants expelled from Spain in the Middle Ages. Slovakian families and a family of Polish origin show another unique haplotype. The haplotypes in families from Germany, Sicily, Austria, and Japan are different from the Mediterranean or eastern European haplotypes. On the basis of this study, we conclude that founder effect and independent mutational events are responsible for the current geographic distribution of hereditary CJD associated with the 200K mutation. (+info)Physicochemical consequences of amino acid variations that contribute to fibril formation by immunoglobulin light chains. (8/3010)
The most common form of systemic amyloidosis originates from antibody light chains. The large number of amino acid variations that distinguish amyloidogenic from nonamyloidogenic light chain proteins has impeded our understanding of the structural basis of light-chain fibril formation. Moreover, even among the subset of human light chains that are amyloidogenic, many primary structure differences are found. We compared the thermodynamic stabilities of two recombinant kappa4 light-chain variable domains (V(L)s) derived from amyloidogenic light chains with a V(L) from a benign light chain. The amyloidogenic V(L)s were significantly less stable than the benign V(L). Furthermore, only the amyloidogenic V(L)s formed fibrils under native conditions in an in vitro fibril formation assay. We used site-directed mutagenesis to examine the consequences of individual amino acid substitutions found in the amyloidogenic V(L)s on stability and fibril formation capability. Both stabilizing and destabilizing mutations were found; however, only destabilizing mutations induced fibril formation in vitro. We found that fibril formation by the benign V(L) could be induced by low concentrations of a denaturant. This indicates that there are no structural or sequence-specific features of the benign V(L) that are incompatible with fibril formation, other than its greater stability. These studies demonstrate that the V(L) beta-domain structure is vulnerable to destabilizing mutations at a number of sites, including complementarity determining regions (CDRs), and that loss of variable domain stability is a major driving force in fibril formation. (+info)
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amyloid
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Drusen deposits associated with aging
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The most pathogenic transthyretin variant, L55P, forms amyloid fibrils under acidic conditions and protofilaments under...
Fibrinogen Amyloidosis: Article Review (2012) - Amyloid diseases of the heart: Current and future therapies
Islet amyloid polypeptide (IAPP) and pancreatic islet amyloid deposition in diabetic and non-diabetic patients. - PubMed - NCBI
Assessment of the Inhibitory Effect of Rifampicin on Amyloid Formation of Hen Egg White Lysozyme: Thioflavin T Fluorescence...
Dipòsit Digital de la Universitat de Barcelona: Role of cellular prion protein in interneuronal amyloid transmission
Revealing the secondary structural changes of amyloid β peptide by probing the spectral fingerprint characters - Wang - 2013 -...
Pharmaceuticals | Free Full-Text | Neuroactive Multifunctional Tacrine Congeners with Cholinesterase, Anti-Amyloid Aggregation...
Plus it
Biophysical studies on aggregation processes and amyloid fibrils with focus on Alzheimers disease
Amyloid plaque synonyms, amyloid plaque antonyms - FreeThesaurus.com
Accused of complicity in Alzheimers, amyloid proteins may be getting a bad rap, study finds | News Center | Stanford Medicine
Renal amyloidosis revisited: amyloid distribution, dynamics and biochemical type : Nephrology Dialysis Transplantation - oi
Biomedical Advances
Amyloid fibril formation propensity is inherent into the hexapeptide tandemly repeating sequence of the central domain of...
Aß40 displays amyloidogenic properties in the non-transgenic mouse brain but does not exacerbate Aß42 toxicity in Drosophila |...
Amyloid domains in the cell nucleus controlled by nucleoskeletal protein lamin B1 reveal a new pathway of mercury neurotoxicity...
Competing discrete interfacial effects are critical for amyloidogenesis. - Oxford Neuroscience
Inhibition of the Formation of Amyloid-Like Fibrils with Spices, Especially Cloves | Springer for Research & Development
A Sequential Assignment Procedure for Proteins that have Intermediate Line Widths in MAS NMR Spectra: Amyloid Fibrils of Human...
Neurotoxic and gliotrophic activity of a synthetic peptide homologous to Gerstmann-Sträussler-Scheinker disease amyloid protein...
In Vivo Visualization of Amyloid Deposits in the Heart with 11C-PIB and PET | Journal of Nuclear Medicine
A molecular dynamics approach to the structural characterization of amyloid aggregation | Caflisch - UZH
MedicalResearch.com | Traumatic Brain Injury: PET Scanning to Detect Amyloid Deposition, Possible Dementia Risk
2DIR Spectroscopy of Human Amylin Fibrils Reflects Stable β-Sheet Structure | Zanni Group
Methylene blue inhibits amyloid Aβ oligomerization by promoting fibrillization<...
Prion protein insertional mutations increase aggregation propensity but not fiber stability | BMC Biochemistry | Full Text
A Rare Case of Systemic AL Amyloidosis with Muscle Involvement: A Misleading Diagnosis
Amyloid degeneration | definition of amyloid degeneration by Medical dictionary
Degradation of fibrillar forms of Alzheimers amyloid β-peptide by macrophages<...
STUDY OF AMYLOID FIBRILLATION OF REGULAR INSULIN: INHIBITION BY AROMATIC COMPOUNDS - Iranian Journal of Diabetes and Metabolism
Partially crystalline order in biological macromolecules - Page 2 - International Discussion Meeting on Polymer Crystallization...
Familial amyloid polyneuropathy
... , also called transthyretin-related hereditary amyloidosis, transthyretin amyloidosis ... Familial amyloid polyneuropathy. From Wikipedia, the free encyclopedia. (Redirected from Transthyretin-related hereditary ... Adams, D; Cauquil, C; Labeyrie, C (October 2017). "Familial amyloid polyneuropathy". Current Opinion in Neurology. 30 (5): 481- ... Scott LJ (August 2014). "Tafamidis: a review of its use in familial amyloid polyneuropathy". Drugs. 74 (12): 1371-8. doi: ...
Oleocanthal
Beta-amyloid[edit]. Studies in an animal model suggest that oleocanthal can reduce the accumulation of β-amyloid proteins via ... "Olive-Oil-Derived Oleocanthal Enhances β-Amyloid Clearance as a Potential Neuroprotective Mechanism against Alzheimer's ...
Florbetaben (18F)
β-amyloid is a key neuropathological hallmark of AD, so markers of β-amyloid plaque accumulation in the brain are useful in ... β-amyloid plaques in the brain. It is indicated for Positron Emission Tomography (PET) imaging of β-amyloid neuritic plaque ... Alzheimer's disease and amyloid-beta PET imaging[edit]. More than 44 million people worldwide have been diagnosed with some ... 2011). "Amyloid imaging with (18)F-florbetaben in Alzheimer disease and other dementias". Journal of Nuclear Medicine. 52 (8): ...
Abyssinian cat
... a kidney disorder due to a mutation in the AA amyloid protein gene, has been seen in Abyssinians.[11] The Abyssinian has had ...
Gram stain
... ing is a bacteriological laboratory technique[4] used to differentiate bacterial species into two large groups (gram-positive and gram-negative) based on the physical properties of their cell walls.[5][page needed] Gram staining is not used to classify archaea, formerly archaeabacteria, since these microorganisms yield widely varying responses that do not follow their phylogenetic groups.[6] The Gram stain is not an infallible tool for diagnosis, identification, or phylogeny, and it is of extremely limited use in environmental microbiology. It is used mainly to make a preliminary morphologic identification or to establish that there are significant numbers of bacteria in a clinical specimen. It cannot identify bacteria to the species level, and for most medical conditions, it should not be used as the sole method of bacterial identification. In clinical microbiology laboratories, it is used in combination with other traditional and molecular techniques to identify bacteria. Some ...
Ziehl-Neelsen stain
The genus Mycobacterium is a slow growing bacteria, made up of small rods that are slightly curved or straight, and are considered to be gram positive. Some types of Mycobacteria form branches or filaments. Some mycobacteria are free-living saprophytes, but many are pathogens that cause disease in animals and humans. Mycobacterium bovis causes tuberculosis in cattle. Since tuberculosis can be spread to humans, milk is pasteurized to kill any of the bacteria.[1]Some Mycobacteria species that cause disease in humans include Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium marinum, Mycobacterium bovis, Mycobacterium africanum and members of the Mycobacterium avium complex. Mycobacterium tuberculosis is a species of Mycobacterium that causes tuberculosis (TB). Mycobacterium tuberculosis is an airborne bacterium that typically infects the human lungs.[2][3] Symptoms of TB include a bad cough, chest pain, fatigue, weight loss, no appetite, chills, fever and night sweats.[4] The typical ...
Staining
The preparatory steps involved depend on the type of analysis planned; some or all of the following procedures may be required.. Fixation-which may itself consist of several steps-aims to preserve the shape of the cells or tissue involved as much as possible. Sometimes heat fixation is used to kill, adhere, and alter the specimen so it accepts stains. Most chemical fixatives (chemicals causing fixation) generate chemical bonds between proteins and other substances within the sample, increasing their rigidity. Common fixatives include formaldehyde, ethanol, methanol, and/or picric acid. Pieces of tissue may be embedded in paraffin wax to increase their mechanical strength and stability and to make them easier to cut into thin slices.. Permeabilization involves treatment of cells with (usually) a mild surfactant. This treatment dissolves cell membranes, and allows larger dye molecules into the cell's interior.. Mounting usually involves attaching the samples to a glass microscope slide for ...
Bruger:Drlectin/sandkasse1, den frie encyklopædi
Amyloid beta is produced in the brain by enzymes that divide a larger protein - the amyloid precursor protein (APP) - into ... AMYLOID BETA[redigér , redigér wikikode]. One of the most common areas of research in the fight against Alzheimer's disease ... focuses on amyloid beta, the sticky proteins that clump together in the brain, forming plaques that choke nerve cells and ... resulting in the production of amyloid beta [[4]] [[5]] ...
Plaque
Amyloid plaque. *Atheroma or atheromatous plaque, a buildup of deposits within the wall of an artery ...
Neurodegeneration
... called beta-amyloid (also written as A-beta or Aβ). Beta-amyloid is a fragment from a larger protein called amyloid precursor ... beta amyloid: the major component of senile plaques in Alzheimer's disease.. *prion: main component of prion diseases and ... Transglutaminase substrates: Amyloid-beta, tau, alpha-synuclein and huntingtin have been proved to be substrates of ... Ohnishi S, Takano K (March 2004). "Amyloid fibrils from the viewpoint of protein folding". Cell. Mol. Life Sci. 61 (5): 511-24 ...
Choroba Alzheimera, wolna encyklopedia
Amyloid imaging in aging and dementia: Testing the amyloid hypothesis in vivo. „Behav Neurol". 21 (1), s. 117-28, 2009. DOI: ... a b Ohnishi S, Takano K. Amyloid fibrils from the viewpoint of protein folding. „Cell. Mol. Life Sci.". 61 (5), s. 511-24, 03 ... amyloid precursor protein, prekursorowe białko amyloidu) na chromosomie 21. Informacja ta wiąże się z prawie pewnym ... Homeostatyczna naprawa mieliny przyczynia się do rozwoju depozytów białkowych, takich jak beta-amyloid czy tau[52][53][54]. ...
Alzheimer's disease
Amyloid hypothesis. In 1991, the amyloid hypothesis postulated that extracellular amyloid beta (Aβ) deposits are the ... Enzymes act on the APP (amyloid precursor protein) and cut it into fragments. The beta-amyloid fragment is crucial in the ... September 2015). "Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy". Nature. 525 (7568): ... called amyloid beta (Aβ). Aβ is a fragment from the larger amyloid precursor protein (APP). APP is a transmembrane protein that ...
Aspartic protease
Other/ungrouped: Amyloid precursor protein secretase *Alpha secretase. *Beta-secretase 1. *Beta-secretase 2 ...
Proteasome endopeptidase complex
Other/ungrouped: Amyloid precursor protein secretase *Alpha secretase. *Beta-secretase 1. *Beta-secretase 2 ...
Dipeptidyl peptidase-4
Other/ungrouped: Amyloid precursor protein secretase *Alpha secretase. *Beta-secretase 1. *Beta-secretase 2 ...
User:RostyslavZvanych/The a-ketoglutarate dehydrogenase complex in Alzheimer's disease
In addition, thiamine deficiency and oxidative stress can be linked to the formation of the beta-amyloid(Aβ) plaques, and this ... In general, Aβ peptide is produced by the cleavage of the parental amyloid precursor protein (APP) that is located at plasma ... Figure 1: The resulted neuritic plaques of beta-amyloid (Aβ) peptide and neurofibrillary tangles of tau protein in brain ... The hallmarks of AD are neuritic plaques of beta-amyloid (Aβ) peptide and neurofibrillary tangles (NFTs) of tau protein in ...
Cathepsin A
Other/ungrouped: Amyloid precursor protein secretase *Alpha secretase. *Beta-secretase 1. *Beta-secretase 2 ...
Beta-secretase 1
Drugs to block this enzyme (BACE inhibitors) in theory would prevent the buildup of beta-amyloid and (per the Amyloid ... Beta-secretase 1 (BACE1), also known as beta-site amyloid precursor protein cleaving enzyme 1, beta-site APP cleaving enzyme 1 ... amyloid-beta binding. • beta-aspartyl-peptidase activity. • GO:0001948 protein binding. • enzyme binding. • hydrolase activity ... amyloid-beta metabolic process. • membrane protein ectodomain proteolysis. • modulation of chemical synaptic transmission. • ...
Carboxypeptidase T
Other/ungrouped: Amyloid precursor protein secretase *Alpha secretase. *Beta-secretase 1. *Beta-secretase 2 ...
阿茲海默症 - 维基百科,自由的百科全
1991年,學者提出類澱粉胜肽假說,認為β類澱粉胜肽(英语:Beta amyloid)(Aβ)在大腦堆積可能是導致阿茲海默症的根本原因[79][80]。根據研究發現表現Aβ的前類澱粉蛋白質基因(APP)位在第21對染色體
AL amyloidosis
Amyloid light-chain (AL) amyloidosis, also known as primary amyloidosis, is the most common form of systemic amyloidosis in the ... These light chains come together to form amyloid deposits which can cause serious damage to different organs.[2][3] Abnormal ... "BU: Amyloid Treatment & Research Program". Archived from the original on 2008-07-20.. ... Both blood and the urine can be tested for the light chains, which may form amyloid deposits, causing disease. However, the ...
PSEN1
Beta-amyloid production[edit]. Transgenic mice that over-expressed mutant presenilin-1 show an increase of beta-amyloid-42(43) ... amyloid-beta formation. • amyloid precursor protein metabolic process. • neutrophil degranulation. • regulation of canonical ... A 5-fold drop of amyloid peptide was observed, suggesting that deficiency of presenilin-1 can down regulate amyloid and ... from amyloid precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease.[6] ...
Amylin
Amyloid deposits deriving from islet amyloid polypeptide (IAPP, or amylin) are commonly found in pancreatic islets of patients ... It is thought that proIAPP forms the first granules that allow for IAPP to aggregate and form amyloid which may lead to amyloid ... Paulsson JF, Westermark GT (July 2005). "Aberrant processing of human proislet amyloid polypeptide results in increased amyloid ... "Entrez Gene: IAPP islet amyloid polypeptide".. *^ a b c Higham CE, Hull RL, Lawrie L, Shennan KI, Morris JF, Birch NP, Docherty ...
乙醯膽鹼酯酶 - 維基百科,自由的百科
beta-amyloid binding. · acetylcholinesterase activity. · acetylcholinesterase activity. · carboxylesterase activity. · ... amyloid precursor protein metabolic process. · neurotransmitter receptor biosynthetic process. · regulation of dendrite ... Pakaski M, Kasa P. Role of acetylcholinesterase inhibitors in the metabolism of amyloid precursor protein.. Current drug ...
Beta cell
Amylin, also known as islet amyloid polypeptide (IAPP).[17] The function of amylin is to slow the rate of glucose entering the ...
Early-onset Alzheimer's disease
Beta-amyloid is a small piece of a larger protein called the amyloid precursor protein (APP). Once APP is activated it is cut ... Deposits of amyloid can be seen in sections of brain tissue. This amyloid protein forms plaques and neurofibrillary tangles ... One of the fragments produced in this cutting process is β-amyloid. β-amyloid is "stickier" than any other fragment produced ... "Increased β-amyloid release and levels of amyloid precursor protein (APP) in fibroblast cell lines from family members with the ...
Memory and aging
However, a similar amount of amyloid plaque was found.[18] More recent research has extended established findings of age ...
endoplasmic reticulum
"The ER stress factor XBP1s prevents amyloid-beta neurotoxicity". Human Molecular Genetics. 20 (11): 2144-60. doi:10.1093/hmg/ ...
Bulbocapnine
... is thus a potential therapeutic under the amyloid hypothesis.[4] According to the Dorlands Medical Dictionary, it ... it is reported to be an inhibitor of amyloid beta protein (Aβ) fiber formation, whose presence is a hallmark of Alzheimer's ... "New class of inhibitors of amyloid-beta fibril formation. Implications for the mechanism of pathogenesis in Alzheimer's ...
Apoptosis
"Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect". Frontiers in Physiology. 5: 522. doi:10.3389/ ...
Alzheimer's Brain Plaques - Alzheimer's Association
Explore an interactive diagram of beta-amyloid formation and how they contribute to the development of plaques in the ... Beta-amyloid is chemically "sticky" and gradually builds up into plaques.. The most damaging form of beta-amyloid may be groups ... Plaques form when protein pieces called beta-amyloid (BAY-tuh AM-uh-loyd) clump together. Beta-amyloid comes from a larger ...
Amyloid | SpringerLink
2011) Amyloid. In: Khan M.G. (eds) Encyclopedia of Heart Diseases. Humana Press. * .RIS Papers ... Gertz MA, Skinner M, Connors LH et al (1985) Selective binding of nifedipine to amyloid fibrils. Am J Cardiol 55:1646PubMed ... Rubinow A, Skinner M, Cohen AS (1981) Digoxin sensitivity in amyloid cardiomyopathy. Circulation 63:1285-1288PubMedGoogle ... Pepys MB, Herbert J, Hutchinson WL et al (2002) Targeted pharmacological depletion of serum amyloid P component for treatment ...
Familial amyloid polyneuropathy - Wikipedia
Familial amyloid polyneuropathy, also called transthyretin-related hereditary amyloidosis, transthyretin amyloidosis ... Familial amyloid polyneuropathy. From Wikipedia, the free encyclopedia. (Redirected from Transthyretin-related hereditary ... Adams, D; Cauquil, C; Labeyrie, C (October 2017). "Familial amyloid polyneuropathy". Current Opinion in Neurology. 30 (5): 481- ... Scott LJ (August 2014). "Tafamidis: a review of its use in familial amyloid polyneuropathy". Drugs. 74 (12): 1371-8. doi: ...
Amyloid Proteins | SpringerLink
Cutting-edge and authoritative, Amyloid Proteins: Methods and Protocols, Third Edition is a valuable resource for both students ... Mapping Amyloid Regions in Gad m 1 with Peptide Arrays Rosa Sánchez, Javier Martínez, Laura Montoya, Milagros Castellanos, ... The chapters in this book are divided into three parts: Part One covers in vitro assays that focus on a variety of amyloids and ... Part Two describes cell culture models and assays, and Part Three explores methods on how to extract amyloid from tissue, its ...
The amyloid hypothesis on trial
Glenner thought that amyloid-β might be the cause of Alzheimers disease, but the amyloid hypothesis did not take off until the ... The fact that such plaques consist of amyloid-β, combined with the discovery of mutations that increase amyloid-β aggregation, ... Even the staunchest supporters of the amyloid hypothesis think that amyloid-β is not the only target worthy of intervention, ... the amyloid hypothesis, which is the assumption that accumulation of the peptide amyloid-β is the main cause of the condition. ...
Amyloid | Newsroom - McGill University
What is amyloid arthropathy?
encoded search term (What is amyloid arthropathy?) and What is amyloid arthropathy? What to Read Next on Medscape. Related ... A primer of amyloid nomenclature. Amyloid. 2007 Sep. 14(3):179-83. [Medline]. ... had amyloid deposition. At 10-year follow-up, only 2 patients had systemic amyloidosis diagnosed after amyloid was discovered ... What is amyloid arthropathy?. Updated: May 09, 2019 * Author: Robert O Holmes, Jr, DO; Chief Editor: Herbert S Diamond, MD more ...
Amyloid Neuropathy
Treatment of amyloid neuropathies is directed at both preventing further deposition of amyloid in peripheral nerves and ... Amyloid Neuropathy. Disorders of peripheral nerves are the most common neurological complications of systemic amyloidosis; an ... Diagnosis of amyloid neuropathies is based on history, clinical examination and supporting laboratory investigations. These ... Depending on the type of amyloid protein, patients may benefit from liver or bone marrow transplant. Neuropathic pain due to ...
What is prolactin amyloid (Apro)?
... prolactin or prolactin fragments are found in the pituitary amyloid. This condition is often observed in elderly people and has ... encoded search term (What is prolactin amyloid (Apro)?) and What is prolactin amyloid (Apro)? What to Read Next on Medscape. ... In prolactin amyloid (Apro), prolactin or prolactin fragments are found in the pituitary amyloid. This condition is often ... A primer of amyloid nomenclature. Amyloid. 2007 Sep. 14(3):179-83. [Medline]. ...
Amyloid Cascade Hypothesis
The amyloid cascade hypothesis postulates that the initial event which triggers neuronal degradation in Alzheimers disease is ... What is amyloid?. The function of amyloid is not yet fully understood; however, it has been shown to contribute to several ... The amyloid plaques previously described are the products of amyloid-β (Aβ) accumulation. These Aβ fragments are generated from ... What is the amyloid cascade hypothesis?. The amyloid cascade hypothesis was initially suggested in 1992. This theory postulates ...
Hereditary cerebral amyloid angiopathy: MedlinePlus Genetics
Hereditary cerebral amyloid angiopathy is a condition that can cause a progressive loss of intellectual function (dementia), ... Genetic Testing Registry: Cerebral amyloid angiopathy, APP-related *Genetic Testing Registry: Hereditary cerebral amyloid ... Hereditary cerebral amyloid angiopathy caused by mutations in the APP, CST3, or ITM2B gene is inherited in an autosomal ... Mutations in the APP gene are the most common cause of hereditary cerebral amyloid angiopathy. APP gene mutations cause the ...
Amyloid, Prions, and Other Protein Aggregates - Google Books
Latest Alzheimer's Flop Raises Doubts About 'Amyloid Hypothesis'
Is it time to rethink the notion that amyloid deposits in the brain drive this disease? ... The hope was that if the drug could eliminate soluble amyloid-beta-the protein blamed for the brain plaques that form in ... The hope was that if the drug could eliminate soluble amyloid-beta-the protein blamed for the brain plaques that form in ... "While the results of Expedition3 were not what we had hoped they would be, we believe the amyloid hypothesis should continue to ...
Pathogenetic mechanisms of amyloid A amyloidosis | PNAS
2000) Amyloid formation in the rat: Adenoviral expression of mouse serum amyloid A proteins. Amyloid 7(1):32-40. ... 1997) Amyloid deposition is delayed in mice with targeted deletion of the serum amyloid P component gene. Nat Med 3(8):855-859. ... Deposition of AA amyloid in humans may thus also be triggered by such an amyloid fibril seed, but it has not hitherto been ... Significant minor amyloid deposits were also present in the kidneys, heart, and gut (Fig. S2). The total amyloid load was much ...
Alzheimer's amyloid protein development halted in mice
Treatment with a new compound that precisely targets and blocks only amyloid precursor protein reduced plaque accumulation by ... The researchers explain that other experimental drugs that tackle amyloid proteins target the enzymes that cleave beta-amyloid ... "Alzheimers amyloid protein development halted in mice." Medical News Today. MediLexicon, Intl., 30 Apr. 2015. Web.. 23 Jan. ... 2-week treatment led to 50% reduction in amyloid plaques in mice. Prof. Dewji - who is also president and CEO of Cenna, the ...
Engineering self-assembling amyloid fibers | EurekAlert! Science News
Amyloid proteins, for example, can self-assemble into the tangled plaques associated with Alzheimers disease -- but can also ... Davis and Rice University have now come up with methods to manipulate natural proteins so that they self-assemble into amyloid ... Engineering self-assembling amyloid fibers. University of California - Davis. Journal. ACS Nano. Funder. UC Davis RISE. ... engineering-self-assembling-amyloid-protein-surfaces/. More in Chemistry & Physics. * Chocolate muddles cannabis potency ...
Alzheimer's Drug Shows Promise for Amyloid Plaque Reduction
... a drug that clears amyloid plaque from the brain, halting the disease. ... The drugmakers themselves have said that in 81 percent of the group taking the highest dose of BAN2401, the amount of amyloid ... showed how the drug not only cleared out significant amounts of amyloid plaque (a hallmark of the disease) but also seemed to ...
Temperature dependence of amyloid β-protein fibrillization | PNAS
Temperature dependence of amyloid β-protein fibrillization. Yoko Kusumoto, Aleksey Lomakin, David B. Teplow, George B. Benedek ... Temperature dependence of amyloid β-protein fibrillization. Yoko Kusumoto, Aleksey Lomakin, David B. Teplow, George B. Benedek ... Temperature dependence of amyloid β-protein fibrillization. Yoko Kusumoto, Aleksey Lomakin, David B. Teplow, and George B. ... Fibrillogenesis of the amyloid β-protein (Aβ) is believed to play a central role in the pathogenesis of Alzheimers disease. ...
Pro-islet amyloid polypeptide (IPR000443) | InterPro | EMBL-EBI
This entry represents the propeptide (Pro-islet amyloid polypeptide) prior to cleavage into islet amyloid polypeptide. ... Islet amyloid polypeptide (IAPP) (also known as diabetes-associated peptide or amylin) is a pancreatic islet hormone that is ... stored with insulin in beta cell granules [PMID: 2192709]. IAPP has a propensity to form islet cell-disrupting amyloid deposits ...
Amyloid beta A4 protein (IPR028866) | InterPro | EMBL-EBI
Amyloid-beta is required for neuronal function, but can aggregate to form amyloid plaques that seem to disrupt brain cells by ... Two of the main isoforms, amyloid-beta40 (Abeta40) and amyloid-beta42 (Abeta42), are found prominently in the extracellular ... Amyloid beta A4 protein (also known as APP or A4) consists of a large N-terminal extracellular region containing heparin- ... The amyloid precursor protein and postnatal neurogenesis/neuroregeneration.. Biochem. Biophys. Res. Commun. 341 1-5 2006 ...
Mechanism for Amyloid-beta Accumulation in Alzheimer's Disease
Mechanism for Amyloid-beta Accumulation in Alzheimers Disease Mechanism for Amyloid-beta Accumulation in Alzheimers Disease ... which normally removes amyloid-beta from the brain. The copper accumulation was also linked with higher brain amyloid-beta ... Low levels of copper disrupt brain amyloid-beta homeostasis by altering its production and clearance. Proc Natl Acad Sci U S A ... An NIEHS grantee and colleagues report that low levels of copper can accumulate in the brain, leading to amyloid-beta plaques ...
Alzheimer's, Memory Loss and Beta Amyloid.
The effect of the buildup of beta amyloid in the brain, caused by a variation of a gene known as CYP46, is memory loss better ... The effect of the buildup of beta amyloid in the brain, caused by a variation of a gene known as CYP46, is memory loss better ... People who suffer from Alzheimers more often have high levels of beta amyloid which collect in clumps, called senile plaques ... Most researchers now agree that beta amyloid buildup is most certainly involved in the disruption of memory and thought. ...
Amyloid Goiter Secondary to Ulcerative Colitis
Diffuse amyloid goiter (AG) is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated ... Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, ... Amyloid goiter is clinically defined as the deposition of amyloid in the thyroid gland in such quantities as to produce an ... To date, an approximate total of 85 cases of amyloid goiter have been reported in the literature. Deposition of amyloid in the ...
β-Amyloid (4G8) | ALZFORUM
Soluble Amyloid Oligomers | ALZFORUM
amyloid beta - NaturalNews.com
Amyloid - Wikipedia
Bacterial Inclusion Bodies Contain Amyloid-Like Structure at SciVee Amyloid Cascade Hypothesis Amyloid: Journal of Protein ... November 2000). "Amyloid fibril formation by A beta 16-22, a seven-residue fragment of the Alzheimers beta-amyloid peptide, ... The "stacks" of beta sheet are short and traverse the breadth of the amyloid fibril; the length of the amyloid fibril is built ... Functional amyloid in Homo sapiens: Intralumenal domain of melanocyte protein PMEL Peptide/protein hormones stored as amyloids ...
amyloid facts, information, pictures | Encyclopedia.com articles about amyloid
Make research projects and school reports about amyloid easy with credible articles from our FREE, online encyclopedia and ... amyloid (am-i-loid) n. a glycoprotein, resembling starch, that is deposited in the internal organs in amyloidosis. β-amyloid ... amyloid A Dictionary of Plant Sciences © A Dictionary of Plant Sciences 1998, originally published by Oxford University Press ... amyloid A Dictionary of Biology © A Dictionary of Biology 2004, originally published by Oxford University Press 2004. ...
Amyloid formation: functional friend or fearful foe? - PubMed - NCBI
Finally, the role of amyloid formation in bacteria will be reviewed. The recent finding that bacteria can make amyloid in a ... However, it is becoming increasingly clear that amyloid is also present in the healthy setting; for example nontoxic amyloid ... Amyloid formation: functional friend or fearful foe?. Bergman P1, Roan NR2,3, Römling U4, Bevins CL5, Münch J6,7. ... The role of amyloid in health and disease is beginning to be unravelled, and here, we will review some of the most recent ...
Islet amyloid polypeptide and type 2 diabetes. - PubMed - NCBI
Islet amyloid polypeptide (IAPP; amylin), the major component of islet amyloid, is co-secreted with insulin from beta-cells. In ... have been proposed to contribute to the development of islet amyloid deposits. Inhibitors of islet amyloid fibril formation ... Islet amyloid polypeptide and type 2 diabetes.. Marzban L1, Park K, Verchere CB. ... The mechanism(s) responsible for islet amyloid formation in type 2 diabetes is still unclear but it appears that an increase in ...
PeptideAmyloidosisPeptidesPrecursorClearing amyloid-betaAccumulationAggregatesProduction of beta-amyloidHypothesisDeposition of amyloidInsolubleResearchersFamilial amyloid polyneIncluding amyloid fibrilsAggregationOligomersAggregateDefinition of amyloidAbnormalFound in the brainsAlzheimer's DiseaseScientistsBrainsClumpsDementiaDetection of amyloid plaquesEvidence of amyloid depositsBrainLevels in cerebrospinal fluidMild cognitivePlaqueMutationsCerebralAlzheimerStructuresClump togetherBeta amyloid buildupForm amyloid fibrilsProteins called amyloidIslet amyloid formationAnti-amyloid strategiesFibril structure predictionPathologyDiseasesGamma-secretaseScansNeurodegeneration
Peptide28
- Their development was guided by an idea that has dominated research on Alzheimer's disease for more than 25 years: the amyloid hypothesis, which is the assumption that accumulation of the peptide amyloid-β is the main cause of the condition. (nature.com)
- Amyloid-β is therefore an obvious therapeutic target - if you can deal with the peptide, then you can treat the condition. (nature.com)
- Some success in preclinical studies evolved into this idea that what we need to do is remove the soluble form of the [amyloid-beta] peptide from the brain. (forbes.com)
- Islet amyloid polypeptide (IAPP) (also known as diabetes-associated peptide or amylin) is a pancreatic islet hormone that is stored with insulin in beta cell granules [ PMID: 2192709 ]. (ebi.ac.uk)
- By this definition, fewer than 25 amyloid-forming proteins have been identified and associated with serious diseases, including amyloid- β peptide (A β ) with Alzheimer's disease (AD), islet amyloid polypeptide (IAPP) with diabetes type 2, and prion protein (PrP) with the spongiform encephalopathies [ 3 ]. (hindawi.com)
- Functional amyloid in Homo sapiens: Intralumenal domain of melanocyte protein PMEL Peptide/protein hormones stored as amyloids within endocrine secretory granules Receptor-interacting serine/threonine-protein kinase 1/3 (RIP1/RIP3) Fragments of prostatic acid phosphatase and semenogelins Functional amyloid in other organisms: Curli fibrils produced by E. coli, Salmonella, and a few other members of the Enterobacteriales (Csg). (wikipedia.org)
- First, the amyloid-forming properties of the antimicrobial peptide human defensin 6 (HD6) will be considered. (nih.gov)
- In type 2 diabetes, this peptide aggregates to form amyloid fibrils that are toxic to beta-cells. (nih.gov)
- If there was pre-symptomatic evidence that amyloid levels were too high in a patient's brain, a GSM might be taken to lower relevant peptide levels and reduce AD risk. (eurekalert.org)
- In this study, we aimed to identify the effects of amyloid-β peptide 42 (amyloid-β42) and phosphorylated tau on the patterns of functional connectomics involved in hippocampal downregulation. (gu.se)
- We identified 48 cognitively unimpaired participants (22 with elevated CSF amyloid-β peptide 42 levels, 15 with elevated CSF phosphorylated tau levels, mean age of 62.705 ± 4.628 years), from the population-based 'Alzheimer's and Families' study, with baseline MRI, CSF biomarkers, APOE genotyping and neuropsychological evaluation. (gu.se)
- In earlier work, Eisenberg's colleague Melinda Balbirnie discovered that a short segment of an amyloid protein - a peptide only seven amino acids long - could form a steric zipper. (emaxhealth.com)
- It wasn't until 1987 that the amyloid peptide was described as the main component of these deposits, known as amyloid plaques. (esrf.fr)
- Amyloid peptide is processed in the extracellular space in the brain and tends to aggregate, forming oligomers that further develop into amyloid fibrils in a nucleation-dependent polymerisation process. (esrf.fr)
- Two different types of amyloid peptide aggregates were found: fibrils (which have been previously described) and - identified for the first time in affected brains - non-fibrillary aggregates with a high component of disordered structure. (esrf.fr)
- Wild-type, full-length (40- and 42-residue) amyloid β-peptide (Aβ) fibrils have been shown by a variety of magnetic resonance techniques to contain cross-β structures in which the β-sheets have an in-register parallel supramolecular organization. (rcsb.org)
- A pathological hallmark of Alzheimer's disease is an accumulation of insoluble plaque containing the amyloid-β peptide of 40-42 amino acid residues 1 . (nature.com)
- Many scientists believe that plaques made of amyloid peptide contribute to brain degeneration in people with Alzheimer's disease. (acs.org)
- Functional amyloids play a beneficial role in a variety of physiologic processes (eg, long-term memory formation, gradual release of stored peptide hormones). (medscape.com)
- Alpha-helix targeting reduces amyloid-beta peptide toxicity. (uniprot.org)
- The amyloid-beta peptide (Abeta) can generate cytotoxic oligomers, and their accumulation is thought to underlie the neuropathologic changes found in Alzheimer's disease. (uniprot.org)
- Immunohistochemical analysis of paraffin-embedded human Alzheimer's brain using β-Amyloid (D12B2) Rabbit mAb in the presence of control peptide (left) or antigen-specific peptide (right). (cellsignal.com)
- The interventions now propose to study the effects of an SSRI ( escitalopram ) on levels of amyloid beta peptide (the major constituent of the plaques) in the cerebrospinal fluid (CSF) of cognitively normal older adults. (clinicaltrials.gov)
- The amyloid-beta (A beta) peptide is a cytotoxic peptide implicated in the pathology of Alzheimer's disease (AD). (nih.gov)
- Gallic acid, or GA, coats the surfaces of amyloid fibrils in semen to prevent HIV infectivity enhancement and coats the peptide precursors to prevent fibril formation. (asbmb.org)
- We propose a working model of A-body biogenesis that includes a role for low complexity ribosomal intergenic spacer RNA (rIGSRNA) and a discrete peptide sequence, the amyloid-converting motif (ACM), found in many proteins that undergo immobilization. (frontiersin.org)
- Peptide and protein hormones are stored in secretory granules in a nonpathological amyloid conformation. (sciencemag.org)
- Accumulations of amyloid β (Aβ) in the brain contribute to the development of Alzheimer's disease, so scientists have long puzzled over why the body produces this peptide. (acs.org)
Amyloidosis28
- Pepys MB, Herbert J, Hutchinson WL et al (2002) Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis. (springer.com)
- Familial amyloid polyneuropathy , also called transthyretin-related hereditary amyloidosis , transthyretin amyloidosis abbreviated also as ATTR (hereditary form), or Corino de Andrade's disease , [1] is an autosomal dominant [2] neurodegenerative disease. (wikipedia.org)
- Amyloid deposition in inflammatory syndromes is amplified by the underlying inflammatory state, significantly increasing morbidity and mortality, especially in the case of renal amyloidosis. (medscape.com)
- In a pathology review of 124 patients undergoing carpal tunnel release without a previous diagnosis or clinical signs of amyloidosis, 82% had amyloid deposition. (medscape.com)
- At 10-year follow-up, only 2 patients had systemic amyloidosis diagnosed after amyloid was discovered in their tenosynovium. (medscape.com)
- Amyloidosis can affect peripheral sensory, motor or autonomic nerves and deposition of amyloid lead to degeneration and dysfunction in these nerves. (hopkinsmedicine.org)
- Kishida D, Okuda Y, Onishi M, Takebayashi M, Matoba K, Jouyama K. Successful tocilizumab treatment in a patient with adult-onset Still's disease complicated by chronic active hepatitis B and amyloid A amyloidosis. (medscape.com)
- In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis. (hindawi.com)
- Amyloidosis is a general term describing a group of diseases characterized by the deposition of an insoluble, proteinaceous, amorphous, and eosinophilic material, called amyloid, in the extracellular matrix of some organs and tissues [ 1 ]. (hindawi.com)
- Primary amyloidosis is characterized by the deposition of amyloid L (AL), which is the major fibrillary protein originating from the light chain components of immunoglobulins, whereas secondary amyloidosis is characterized by the deposition of amyloid A (AA), which constitutes a portion of the acute-phase serum amyloid A (SAA) protein produced by the liver during inflammation. (hindawi.com)
- Deposition of amyloid in the thyroid gland may coexist with systemic amyloidosis, with medullary thyroid carcinoma, and less commonly with primary amyloidosis involving the thyroid gland. (hindawi.com)
- Such amyloids have been associated with (but not necessarily as the cause of) more than 50 human diseases, known as amyloidosis, and may play a role in some neurodegenerative disorders. (wikipedia.org)
- The International Society of Amyloidosis classifies amyloid fibrils and their associated diseases based upon associated proteins (for example ATTR is the group of diseases and associated fibrils formed by TTR). (wikipedia.org)
- amyloid Tissue consisting of protein fibrils that may accumulate between cells in various animal tissues, especially in the disorder amyloidosis . (encyclopedia.com)
- amyloid ( am -i-loid) n. a glycoprotein, resembling starch, that is deposited in the internal organs in amyloidosis. (encyclopedia.com)
- Amyloid formation has been most studied in the context of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, as well as in amyloidosis. (nih.gov)
- The Stanford Amyloid Center comprises a comprehensive team of physicians, scientists, nurses, and counselors dedicated to improving the care of patients with amyloidosis. (stanford.edu)
- Since its founding in 2008, the Stanford Amyloid Center has grown into one of the largest treatment centers for amyloidosis in the world and the largest in the western United States. (stanford.edu)
- Areas of active clinical research relevant to cardiac amyloidosis include cardiac imaging that uses magnetic resonance imaging (MRI) and nuclear imaging (using the pyrophosphate or PYP scan), studies examining the biochemical basis of amyloid toxicity, and projects examining the best treatment of patients with cardiac amyloidosis. (bmc.org)
- For further information regarding the program or ongoing research studies, or to refer a patient with amyloidosis, please contact the program office at 617.638.4317 or visit the Amyloid Center Webpage . (bmc.org)
- Beta-Amyloid (A ) peptides, made up of long, insoluble ordered fibers, are glycoproteins deposited extracellularly in tissues in amyloidosis. (anaspec.com)
- For instance, in one type of amyloidosis known as AL, chemotherapy is required, but chemo is inappropriate and potentially harmful to patients with other amyloid conditions," Dr Hill said. (edu.au)
- Amyloidosis results from the accumulation of pathogenic amyloids-most of which are aggregates of misfolded proteins-in a variety of tissues. (medscape.com)
- Amyloidosis is a clinical disorder caused by extracellular and/or intracellular deposition of insoluble abnormal amyloid fibrils that alter the normal function of tissues. (medscape.com)
- Only 10% of amyloidosis deposits consist of components such as glycosaminoglycans (GAGs), apolipoprotein-E (apoE), and serum amyloid P-component (SAP), while nearly 90% of the deposits consist of amyloid fibrils that are formed by the aggregation of misfolded proteins. (medscape.com)
- The modern era of amyloidosis classification began in the late 1960s with the development of methods to solubilize amyloid fibrils. (medscape.com)
- In a presumed prion-like mechanism, amyloid fibrils have been shown to trigger and accelerate the development of AA amyloidosis in rodent models. (environmental-expert.com)
- The finding of amyloid fibrils in edible avian and mammalian food animal tissues, combined with the inability of cooking temperatures to eliminate their amyloidogenic potential, has led to concerns that products such as pate de foie gras may activate a reactive systemic amyloidosis in susceptible consumers. (environmental-expert.com)
Peptides22
- Writing in the journal PLOS ONE , researchers from the University of California-San Diego (UCSD) School of Medicine and Cenna Biosciences, Inc. describe how they identified compounds that block the production of beta-amyloid peptides in mice. (medicalnewstoday.com)
- The P8 compound in this new study does not act on enzymes - it binds to APP and blocks the process that cuts it up into the smaller amyloid peptides. (medicalnewstoday.com)
- High levels of these peptides, particularly A-beta 42, have been linked to the creation of beta-amyloid plaques in Alzheimer's disease, a neurodegenerative condition that afflicts 5.3 Americans and more than 26 million people worldwide. (eurekalert.org)
- A major pathological feature of Alzheimer's disease is the presence of cerebral senile plaques with aggregated amyloid beta (Aβ) peptides as the main constituent. (kth.se)
- The test for CSF Beta-Amyloid by LC-MS/MS monitors both CSF beta-amyloid 40 (AB40) and 42 (AB42) endogenous peptides, rather than only AB42. (questdiagnostics.com)
- The quantitation of both AB peptides permits the normalization of beta amyloid levels circulating in cerebrospinal fluid in different patients by using a ratio of beta-amyloid 42/beta-amyloid 40, resulting in an improved sensitivity for monitoring cognitive impairment that can progress to Alzheimer's disease. (questdiagnostics.com)
- The causes of Alzheimer's disease (AD) are still unclear, but postmortem examination of patient's brains reveal abundant senile plaques composed of amyloid-beta (Aa) peptides and neurofibrillary tangles formed by filaments of highly phosphorylated tau protein. (sbir.gov)
- By studying peptides from 10 different amyloid-forming proteins, Eisenberg found three different types of variation in the steric zippers. (emaxhealth.com)
- Next, he found that some amyloid-forming peptides were flipped relative to each other - much like two hands folding palm to back-of-hand, rather than palm-to-palm. (emaxhealth.com)
- The technique is particularly useful in the case of amyloid aggregation, since the aggregated peptides/proteins generate very specific and easily identifiable spectroscopic bands in the mid-infrared regions (between 1620 and 1630 cm-1) [2] . (esrf.fr)
- The role of metal cations is also a highly discussed topic in relation to Alzheimer's disease since metals, together with the amyloid peptides, may be involved in a redox reaction that could lead to oxidative stress, which could be related to the development of the disease. (esrf.fr)
- Aβ peptides are produced by the proteolytic cleavage of the transmembrane protein amyloid precursor protein (APP) by enzyme complexes a, β and γ-secretases. (news-medical.net)
- Here we crystallographically characterize designed peptides that assemble into spiraling cross-α amyloid-like structures, which resemble twisted β-amyloid fibrils. (rcsb.org)
- The peptides form helical dimers, stabilized by packing of small and apolar residues, and the dimers further assemble into cross-α amyloid-like fibrils with superhelical pitches ranging from 170 Å to 200 Å. (rcsb.org)
- These peptides are generated as cleavage products 39 to 43 amino acids in length from the membrane protein, Amyloid Precursor Protein (APP) by two proteases, -secretase and γ-secretase. (anaspec.com)
- Heterogeneity at both ends of the peptides is known to affect the toxicity of beta-amyloid peptides. (anaspec.com)
- Amyloid deposits are insoluble and the core component of these plaques are A peptides that are 39 to 42 amino acid residues in length with a molecular mass of approximately 4 kDa. (anaspec.com)
- Polymorphisms that slightly vary native peptides or inflammatory processes set the stage for abnormal protein folding and amyloid fibril deposition. (medscape.com)
- These peptides spontaneously self-assembled in water to form fibril structures (pictured) resembling those that make up the amyloid-β plaques found in the brains of Alzheimer s patients. (phys.org)
- Western blot analysis of the indicated amounts of human Aβ-42 (left) and Aβ-40 (right) peptides using β-Amyloid (D12B2) Rabbit mAb. (cellsignal.com)
- Offering a potential early intervention for Alzheimer's disease (AD), researchers at University of California, San Diego School of Medicine and Cenna Biosciences, Inc. have identified compounds that block the production of beta amyloid peptides in mice. (ucsd.edu)
- The P8 compound does not act on enzymes, but rather binds to APP and in so doing, prevents the larger protein from being processed into smaller amyloid peptides. (ucsd.edu)
Precursor22
- Together with his colleague Caine Wong, Glenner showed that it is derived from a larger protein called amyloid precursor protein (APP), which sits in and crosses the cell membrane. (nature.com)
- Alzheimer's disease can be either sporadic or familial, with common mutations found in amyloid precursor protein (APP) and presenilin genes. (news-medical.net)
- The APP gene provides instructions for making a protein called amyloid precursor protein. (medlineplus.gov)
- In the brain, the amyloid precursor protein plays a role in the development and maintenance of nerve cells (neurons). (medlineplus.gov)
- Additionally, the ITM2B protein may be involved in processing the amyloid precursor protein. (medlineplus.gov)
- She and her colleagues believe it is likely the new drug would have few side effects because of how it acts specifically on one target - amyloid precursor protein (APP). (medicalnewstoday.com)
- The researchers explain that other experimental drugs that tackle amyloid proteins target the enzymes that cleave beta-amyloid from its larger precursor protein APP. (medicalnewstoday.com)
- The amyloid precursor protein and postnatal neurogenesis/neuroregeneration. (ebi.ac.uk)
- Other factors, such as impairment in the processing of proIAPP, the IAPP precursor, have been proposed to contribute to the development of islet amyloid deposits. (nih.gov)
- This is Merck's oral inhibitor of beta secretase or BACE, one of the enzymes (the other principal one is gamma secretase) that cleaves beta-amyloid protein from a larger precursor molecule. (medpagetoday.com)
- We therefore created a free online knowledge database (AMYPdb) dedicated to amyloid precursor proteins and we have performed large scale sequence analysis of the included data. (nih.gov)
- ADAMs family members as amyloid precursor protein α‐secretases. (news-medical.net)
- 1999). Purification and cloning of amyloid precursor protein β-secretase from human brain. (news-medical.net)
- Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice. (gu.se)
- APP23 transgenic mice express mutant human amyloid precursor protein and develop amyloid plaques predominantly in neocortex and hippocampus progressively with age, similar to Alzheimer's disease. (gu.se)
- It decreases the amount of plaque-forming beta-amyloid protein by changing the point at which gamma secretase cleaves the amyloid precursor protein. (thefreedictionary.com)
- Additionally, the gallic acid-coated fibrils prevent the formation of new amyloid fibrils by binding the precursor components and changing their charge characteristics. (asbmb.org)
- Because of the currently perceived role of beta amyloid in disease progression, several investigational drugs have targeted the enzymes that cleave beta amyloid from its larger precursor protein, the aptly named amyloid precursor protein (APP). (ucsd.edu)
- Professor Kenneth Kosik describes the relationship between the amyloid precursor protein (APP) and Alzheimer's disease. (dnalc.org)
- As we go deeper in the study of Alzheimer's disease and move down to the level of the gene, we know that the protein in the senile plaque is encoded by a gene called the amyloid precursor protein gene. (dnalc.org)
- That gene is critically important for the Alzheimer's disease process, not only because it's the product of that gene that forms the plaque but also, in a few rare cases of the disease, mutations in the amyloid precursor gene can lead to early-onset Alzheimer's disease. (dnalc.org)
- Amyloid precursor protein (APP) is expressed in the synapses of neurons and is thought to be responsible for forming and repairing synapses. (dnalc.org)
Clearing amyloid-beta1
- There are also two ongoing trials of solanezumab that could prove valuable, because they address the question of whether clearing amyloid-beta in healthy people who face a high risk of developing Alzheimer's can actually prevent the most debilitating symptoms. (forbes.com)
Accumulation20
- This seeds the accumulation of amyloid-β into larger structures called oligomers. (nature.com)
- The amyloid plaques previously described are the products of amyloid-β (Aβ) accumulation. (news-medical.net)
- Neurodegeneration occurs when changes in APP processing lead to the accumulation of beta-amyloid which goes on to affect surrounding neurons and other tissues, through oxidative damage which affects many other signalling pathways leading ultimately to apoptosis. (bio.net)
- Two potential sources of chronic stress are the accumulation of clumps of beta-amyloid protein in the brain, a known hallmark of Alzheimer's, and diseased arteries which are also linked to dementia. (thefreedictionary.com)
- Objective: Because curcumin's anti-inflammatory properties may protect the brain from neurodegeneration, we studied its effect on memory in non-demented adults and explored its impact on brain amyloid and tau accumulation using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile positron emission tomography (FDDNP-PET). (mendeley.com)
- The FDDNP-PET findings suggest that symptom benefits are associated with decreases in amyloid and tau accumulation in brain regions modulating mood and memory. (mendeley.com)
- While none of the patients exhibited signs of dementia before their deaths, most had moderate to severe accumulation of amyloid-β in their brains. (the-scientist.com)
- But when Collinge and his colleagues looked at the brains of patients who'd died of CJD but had not received cadaver-derived growth hormone treatments, they found no evidence of amyloid-β accumulation in similarly aged individuals. (the-scientist.com)
- They found that adults ages 50 to 59 who had amyloid were twice as likely to develop dementia by the time they reached their 80s, compared with age-matched counterparts with no signs of amyloid accumulation. (auntminnie.com)
- Higher magnification of Figure 1 with perivascular accumulation of amyloid (arrow). (nih.gov)
- Widespread accumulation of amyloid with secondary tubular degeneration and necrosis. (nih.gov)
- Our research was able to detect subtle thinking and memory differences in study participants and these participants had faster amyloid accumulation on brain scans over time, suggesting that amyloid may not necessarily come first in the Alzheimer's disease process," said study author Kelsey R. Thomas, PhD, of the VA San Diego Healthcare System in San Diego. (newswise.com)
- After adjusting for age, education, sex, genetic risk for Alzheimer's disease, and amyloid level at the start of the study, researchers found people with subtle thinking and memory differences had a more rapid accumulation of amyloid compared to people with normal thinking and memory skills. (newswise.com)
- On the other hand, researchers also found that, while people with mild cognitive impairment had more amyloid in their brains at the beginning of the study, they did not have faster accumulation of amyloid when compared to those with normal thinking and memory skills. (newswise.com)
- Canadian researchers found that patients who took medications for vascular conditions, such as high cholesterol levels and blood pressure, had muted results on PET for beta-amyloid accumulation. (auntminnie.com)
- Concurrently, vascular risk factors such as hypertension are believed to contribute to beta-amyloid accumulation and cardiovascular disease. (auntminnie.com)
- The researchers, however, could find no statistically significant associations between vascular risk factors and beta-amyloid accumulation among the adults taking the medications. (auntminnie.com)
- The research team found that amyloid accumulation was faster in persons classified with Obj-SCD than in the cognitively normal group. (ucsd.edu)
- Persons with MCI had more amyloid in their brain at the start of the study, but they did not have faster accumulation of amyloid compared to those with normal cognition. (ucsd.edu)
- The ability to identify those at risk for AD before significant impairment and before or during the phase of faster amyloid accumulation would be a clinical boon, said authors, providing both a way to monitor disease progression and a window of opportunity to apply potential preventive or treatment strategies. (ucsd.edu)
Aggregates11
- Fandrich M. On the structural definition of amyloid fibrils and other polypeptide aggregates. (medscape.com)
- Amyloids are aggregates of proteins characterised by a fibrillar morphology of 7-13 nm in diameter, a β-sheet secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. (wikipedia.org)
- One of the indications of AD is the presence of amyloid-β (Aβ) aggregates in the brains of those afflicted. (aiche.org)
- The fact that these toxic amyloid aggregates have, until now, mainly been described in vitro , makes their identification and characterisation in affected brains one of the major challenges in amyloid research. (esrf.fr)
- A team of researchers from Barcelona in collaboration with scientists from the ESRF have used infrared microscopy at beamline ID21 and at the ALBA synchrotron to characterise the amyloid aggregates in brain samples from patients in advanced stages of Alzheimer's disease. (esrf.fr)
- Tau aggregates also have certain structural similarities to amyloid beta aggregates-yet any good tau tracer needs clearly to distinguish the one from the other. (dana.org)
- Now, scientists report a molecular link between the two diseases in the form of protein aggregates known as amyloids. (scienceblog.com)
- Natural tri- to hexapeptides self-assemble in water to amyloid β-type fiber aggregates by unexpected α-helical intermediate structures. (phys.org)
- Many fatal neurodegenerative diseases such as Alzheimer s, Parkinson, the prion-related diseases, and non-neurodegenerative disorders such as type II diabetes are characterized by abnormal amyloid fiber aggregates, suggesting a common mechanism of pathogenesis. (phys.org)
- One alternative explanation for the results is that the prion aggregates that cause CJD spurred the formation of amyloid-β plaques, a phenomenon called cross-seeding that has been shown in transgenic mice for aggregates of tau and α-synuclein . (the-scientist.com)
- Scientists at IRB Barcelona in collaboration with researchers at the University of Barcelona observe that aggregates of 20 to 100 units of beta-amyloid have a structure that is the most harmful to neurons. (irbbarcelona.org)
Production of beta-amyloid5
- We are blocking the actual production of beta-amyloid in a new way. (medicalnewstoday.com)
- John Morris told MedPage Today that the evidence from past anti-amyloid drug trials had shown convincingly that, when symptoms have developed, it's too late to reverse them by shutting down further production of beta-amyloid protein. (medpagetoday.com)
- The important question is what is the switch in healthy people which leads to the production of beta-amyloid and consequent neurodegeneration. (bio.net)
- AD therapies need to deal with either preventing this switch and hence the production of beta-amyloid (which already successfully exist, through secretase inhibitors and knockout mice models), or by preventing the actions of beta-amyloid once produced (for example antioxidants show clinical benefits in AD). (bio.net)
- We now have a new approach for the treatment of Alzheimer's disease that can arrest the production of beta amyloid very early and specifically," she said. (ucsd.edu)
Hypothesis14
- The amyloid hypothesis has never been universally accepted, and the failed drug trials have only emboldened its critics. (nature.com)
- Glenner thought that amyloid-β might be the cause of Alzheimer's disease, but the amyloid hypothesis did not take off until the discovery of the dominantly inherited mutations that are responsible for the familial forms of the condition. (nature.com)
- What is the amyloid cascade hypothesis? (news-medical.net)
- The amyloid cascade hypothesis was initially suggested in 1992. (news-medical.net)
- Retrieved on December 09, 2019 from https://www.news-medical.net/life-sciences/Amyloid-Cascade-Hypothesis.aspx. (news-medical.net)
- This is sure to disappoint researchers who have been hanging onto the "amyloid hypothesis" of Alzheimer's-the notion that amyloid-beta accumulating in the brain is what drives the disease. (forbes.com)
- The fact that Expedition3 couldn't even replicate those hopeful findings from the two previous trials should raise questions about the amyloid hypothesis , says Michael Murphy, a professor at the Sanders-Brown Center on Aging at the University of Kentucky, and the author of an editorial that accompanies the study in the NEJM . (forbes.com)
- While the results of Expedition3 were not what we had hoped they would be, we believe the amyloid hypothesis should continue to be studied," she said in an e-mailed statement. (forbes.com)
- Even staunch advocates of the so-called amyloid hypothesis in Alzheimer's disease -- which holds that beta-amyloid protein plaques are a key causative factor in the neurodegeneration that underlies the condition -- had changed their thinking. (medpagetoday.com)
- The working hypothesis is that the successful structure will incorporate the elements of an electron-donating group on an aromatic ring (A) attached to an aromatic heterocyclic 5/6 ring system (B/C). Eleven candidates will be synthesized and tested by in vitro homogenate displacement binding against radiolabeled ligand for amyloid protein. (sbir.gov)
- Hardy, J. & Selkoe, D. J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. (nature.com)
- It was another blow to the so-called amyloid hypothesis, which holds that Alzheimer's is the result of clumps of amyloid protein, called plaques, and that preventing their formation or clearing them from the brain might slow or even halt the decline. (xconomy.com)
- The amyloid hypothesis or amyloid cascade model posits that accumulating amyloid protein plaques in the brain kill neurons and gradually impair specific cognitive functions, such as memory, resulting in AD dementia. (ucsd.edu)
- However, many scientists are now questioning the amyloid hypothesis given the large number of clinical trials in which drugs targeted and successfully cleared amyloid from the brain but did not impact the trajectory of cognitive decline. (ucsd.edu)
Deposition of amyloid5
- [ 86 ] Whether causal or just associated, various autoimmune diseases can also predispose to the deposition of amyloid fibrils. (medscape.com)
- Treatment of amyloid neuropathies is directed at both preventing further deposition of amyloid in peripheral nerves and treating painful symptoms. (hopkinsmedicine.org)
- Diffuse amyloid goiter (AG) is an entity characterized by the deposition of amyloid in the thyroid gland. (hindawi.com)
- Amyloid goiter is clinically defined as the deposition of amyloid in the thyroid gland in such quantities as to produce an enlargement in the gland. (hindawi.com)
- 2 , 3 Her FDG-PET scan (A) was incompatible with Alzheimer disease because of sparing of the cingulate gyri (arrows), but amyloid imaging (B) showed substantial diffuse fibrillary deposition of amyloid plaques throughout the brain, a pattern compatible with Alzheimer disease. (cmaj.ca)
Insoluble4
- For example, Biogen is currently testing a drug called aducanumab, which targets the insoluble form of amyloid-beta instead of the soluble form. (forbes.com)
- Amyloid deposits are insoluble and can exert pressure on various vital organs. (encyclopedia.com)
- The A4 protein accumulates extracellularly, both in brain parenchyma and in the walls of blood vessels, generally as amyloid plaques which form aggregate fibril structures and are insoluble on SDS-polyacrylamide gels. (google.com)
- The drug is a monoclonal antibody that binds to solitary, soluble strands of beta-amyloid protein, causing it to be eliminated by the body's waste-clearance mechanisms before they aggregate into insoluble plaques. (medpagetoday.com)
Researchers22
- Researchers proposed that when amyloid-β clumps together to form deposits in the brain, it triggers neurodegenerative processes that lead to the loss of memory and cognitive ability that is observed in Alzheimer's disease. (nature.com)
- Yet amyloid-β is not the only potential cause, and some researchers think that it is time to explore alternative avenues. (nature.com)
- UC Davis researchers have engineered other proteins so they spontaneously form amyloid. (eurekalert.org)
- Researchers at UC Davis and Rice University have now come up with methods to manipulate natural proteins so that they self-assemble into amyloid fibrils. (eurekalert.org)
- Most researchers now agree that beta amyloid buildup is most certainly involved in the disruption of memory and thought. (selfgrowth.com)
- UCLA academic researchers are closer to explaining how vitamin D3 may help the body rid the brain of amyloid beta which is found in the plaques associated with Alzheimer's disease. (bellaonline.com)
- Researchers have analysed Alzheimer's disease brain samples at beamlines ID21 and ID16A, utilising micro-FTIR and X-ray fluorescence microscopy to characterise two types of amyloid plaques with differences in metal ion composition and in their levels of oxidised lipids. (esrf.fr)
- Combining infrared microscopy with X-ray fluorescence (XRF) measured at beamline ID16A allowed the researchers to study the correlation between different types of amyloid deposits and their metal ion composition ( Figure 1 ). (esrf.fr)
- Researchers now broadly accept that its spreading dysfunction in the brain is more closely connected to the massive loss of neurons underlying dementia, compared to the early, slow buildup of amyloid beta plaques. (dana.org)
- Because α-synuclein in melanoma cells may also be found in its soluble, or non-amyloid, form, the researchers performed other in vitro experiments in which they added soluble α-synuclein to the Pmel RPT domain. (scienceblog.com)
- FLICKR, ALLAN AJIFO Examining the brains of recently deceased patients who more than 30 years ago received injections of growth hormone derived from the pituitary glands of cadavers, researchers have found evidence that Alzheimer's disease (AD) may be transmissible via extracts contaminated with amyloid-β. (the-scientist.com)
- Subjects with amyloid-positive PET scans had a 2.3-fold increase in their risk of developing amnestic mild cognitive impairment, compared with those who had negative amyloid results, the researchers found. (auntminnie.com)
- In a small pilot study, a team of US researchers has discovered how vitamin D3, a form of vitamin D, and omega 3 fatty acids may help the immune system clear the brain of amyloid plaques, one of the physical hallmarks of Alzheimer's disease. (medicalnewstoday.com)
- In their earlier work, the researchers showed how certain mechanisms regulated by vitamin D3 help clear amyloid-beta, the abnormal protein found in sticky plaques that clog up the important communication space between brain cells in people with Alzheimer's. (medicalnewstoday.com)
- The researchers incubated the macrophages for a few hours with amyloid beta. (medicalnewstoday.com)
- Now in an Oct. 18 paper in Science , researchers led by Maiken Nedergaard, MD, of the University of Rochester Medical Center in New York, discovered a key reason why - during sleep the brain doubles the rate at which it removes metabolic debris, including amyloid-beta (Abeta). (lww.com)
- Researchers at IRB Barcelona describe for the first time how to prepare a specific type of aggregate of the amyloid-beta protein with the ability to perforate the cell membrane. (irbbarcelona.org)
- Researchers incubated the macrophages with amyloid beta, vitamin D3 and natural or synthetic curcumin. (emaxhealth.com)
- In addition to cell culture experiments, researchers also conducted experiments with mice, engineered to produce large amounts of the human beta amyloid early in life. (ucsd.edu)
- Perhaps most importantly, Köbe and colleagues noted that the findings could have "clinical implications," and that future researchers should be aware that "cardiovascular medication might reduce Alzheimer's risk by lowering arterial stiffness, leading to increased cerebral blood flow and [beta-amyloid] clearance. (auntminnie.com)
- Since it offers a potentially faster and less expensive way to screen people for high amyloid burden than current tests, the researchers hope to make LASSI-L a low-tech tool to assist in medical evaluations and clinical trial recruitment. (nih.gov)
- Writing in the December 30, 2019 online issue of Neurology , researchers at University of California San Diego School of Medicine and Veterans Affairs San Diego Healthcare System report that accumulating amyloid - an abnormal protein linked to neurodegenerative conditions such as Alzheimer's disease (AD) - occurred faster among persons deemed to have 'objectively-defined subtle cognitive difficulties' (Obj-SCD) than among persons considered to be 'cognitively normal. (ucsd.edu)
Familial amyloid polyne2
- Familial amyloid polyneuropathy has an autosomal dominant pattern of inheritance. (wikipedia.org)
- The medication tafamidis has been approved for the treatment of transthyretin familial amyloid polyneuropathy in Europe. (wikipedia.org)
Including amyloid fibrils1
- The tetramer has to dissociate into misfolded monomers to aggregate into a variety of structures including amyloid fibrils. (wikipedia.org)
Aggregation8
- The fact that such plaques consist of amyloid-β, combined with the discovery of mutations that increase amyloid-β aggregation, strongly implicates amyloid-β as the culprit in familial Alzheimer's disease. (nature.com)
- The aggregation of amyloid-β is thought to trigger a cascade of disease-causing processes such as inflammation, tau-tangle formation, synapse dysfunction and cell death, which ultimately leads to dementia. (nature.com)
- This theory postulates that the initial event which triggers neuronal degradation in Alzheimer's disease is enhanced amyloid-β generation and aggregation. (news-medical.net)
- These results help to elucidate the physics of the aggregation process, the chemistry of amyloid inhibitors, and the biology of type 2 diabetes, as well as clarify previously contradictory data. (redorbit.com)
- We generated and analyzed 3,621 amino acid sequence patterns, reporting highly specific patterns for each amyloid family, along with patterns likely to be involved in protein misfolding and aggregation. (nih.gov)
- Amyloid assembly into fibrils is initiated by a conformational transition from random coil to -sheet and a nucleation-dependent aggregation process. (anaspec.com)
- We now have preliminary data that suggest an amyloid from one protein can 'seed' or template amyloid from another, and in the soluble form, α-synuclein prevents Pmel aggregation. (scienceblog.com)
- This is the first time that a method allows scientists to monitor aggregation while simultaneously detect a structural pattern responsible for the toxicity of beta-amyloid aggregation. (irbbarcelona.org)
Oligomers5
- Together, these data imply a high-affinity cell-surface receptor for soluble amyloid-β oligomers on neurons-one that is central to the pathophysiological process in Alzheimer's disease. (nature.com)
- Amyloid-β oligomers bind with nanomolar affinity to PrP C , but the interaction does not require the infectious PrP Sc conformation. (nature.com)
- Natural oligomers of the amyloid-β protein specifically disrupt cognitive function. (nature.com)
- Synaptic targeting by Alzheimer's-related amyloid β oligomers. (nature.com)
- Natural oligomers of the Alzheimer amyloid-β protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. (nature.com)
Aggregate7
- Amyloid-beta is required for neuronal function, but can aggregate to form amyloid plaques that seem to disrupt brain cells by clogging points of cell-cell contact. (ebi.ac.uk)
- Amyloid diseases, such as Alzheimer's disease, type 2 diabetes, cataracts, and the spongiform encephalopathies, all share the common trait that proteins aggregate into long fibers which then form plaques. (redorbit.com)
- Exebryl-1 has been shown to inhibit beta-amyloid protein aggregate formation in brain, as well as disaggregate amyloid plaques that are already present. (thefreedictionary.com)
- When Dean added preformed α-synuclein amyloid to a test tube containing the amyloid-forming region of Pmel (known as the repeat, or RPT, domain), the α-synuclein fibrils stimulated Pmel to aggregate and form a twisted fibril structure that the protein does not normally adopt on its own. (scienceblog.com)
- In this case, α-synuclein inhibited Pmel's ability to self-aggregate and form amyloid in a concentration-dependent manner. (scienceblog.com)
- Molecules of beta amyloid naturally aggregate in a solution, as they appear to do in the brain. (medgadget.com)
- But once the amyloids begin to aggregate into fibrils that resemble "microscopic strands of spaghetti," hydrophobic parts of the metal complex are naturally drawn to them. (medgadget.com)
Definition of amyloid1
- The classical, histopathological definition of amyloid is an extracellular, proteinaceous fibrillar deposit exhibiting β-sheet secondary structure and identified by apple-green birefringence when stained with congo red under polarized light. (wikipedia.org)
Abnormal4
- Exactly what causes the brain to waste away in Alzheimer's disease is not clear, but scientists believe the abnormal amounts of faulty proteins in the form of amyloid plaques and tau tangles found in the brains of people who have died with the disease have something to do with it. (medicalnewstoday.com)
- Amyloid: the Journal of Protein Folding Disorders is a peer-reviewed scientific journal that publishes original research and review articles on all aspects of the protein groups and associated disorders that are classified as amyloidoses as well as other disorders associated with abnormal protein folding. (wikipedia.org)
- Then, controlling for age, we identified the effects of abnormal CSF amyloid-β42 and phosphorylated tau levels on eigenvector centrality during hippocampal CA1 downregulation. (gu.se)
- Four years ago, Howard Hughes Medical Institute investigator David Eisenberg provided the first glimpse of the atomic structure of amyloid fibrils - long filaments of abnormal proteins stacked up inside cells. (emaxhealth.com)
Found in the brains3
- β-amyloid protein has been found in the brains of Alzheimer's patients. (encyclopedia.com)
- An amyloid that circulates in human blood and in cerebrospinal fluid and is deposited into plaques found in the brains of patients with Alzheimer's disease. (thefreedictionary.com)
- Signs of the beta-amyloid protein were found in the brains of seven patients aged 36 to 51 who had died from Creutzfeldt-Jakob Disease (CJD) after receiving growth hormone from the pituitary glands of dead people. (thefreedictionary.com)
Alzheimer's Disease36
- Amyloid and Alzheimer's disease: inside and out. (medscape.com)
- Therefore, it has been suggested that boosting the non-toxic, non-amyloidogenic processing pathway or reducing the toxic amyloidogenic processing pathway may lead to less amyloid-β production and reduce the progression of Alzheimer's disease. (news-medical.net)
- Amyloid proteins, for example, can self-assemble into the tangled plaques associated with Alzheimer's disease -- but similar proteins can also form very useful materials, such as spider silk, or biofilms around living cells. (eurekalert.org)
- Fibrillogenesis of the amyloid β-protein (Aβ) is believed to play a central role in the pathogenesis of Alzheimer's disease. (pnas.org)
- Two of the main isoforms, amyloid-beta40 (Abeta40) and amyloid-beta42 (Abeta42), are found prominently in the extracellular brain deposits associated with Alzheimer's disease (AD) [ PMID: 24312636 ]. (ebi.ac.uk)
- A build-up of amyloid tissue in the brain is a feature of Alzheimer's disease , Creutzfeldt-Jakob disease , and bovine spongiform encephalopathy . (encyclopedia.com)
- The present invention provides an in vitro tissue culture-based assay for amyloid deposition specific for Alzheimer's disease which is suitable for routine drug screening analysis. (google.com)
- The failure of yet another anti-amyloid drug for Alzheimer's disease in phase III trials this summer turned out not to be the strategy's death knell after all. (medpagetoday.com)
- Here's what's happened with drug development for Alzheimer's disease since we published the first 2012 piece on what appeared to be the demise of beta-amyloid as a drug target for symptomatic disease. (medpagetoday.com)
- The March issue of the Journal of Alzheimer's Disease explains that vitamin D3 may trigger specific genes to set off cellular signaling which stimulates the immune system to clear away the dreaded amyloid-beta protein. (bellaonline.com)
- A radiotracer that bound specifically to amyloid would be of great utility in diagnosis, monitoring treatment, and research of such Alzheimer's disease and related gerontological disorders. (sbir.gov)
- Amyloid fibrils are found in more than 20 human diseases, including type II diabetes, Alzheimer's disease, Lou Gehrig's disease, and Creutzfeldt-Jakob disease ( CJD), the human version of mad cow disease. (emaxhealth.com)
- In conclusion, the existence of amyloid deposits with disordered/non-fibrillar structure, coexisting with the typical fibrillary plaques, has been described for the first time in situ in human brains with advanced Alzheimer's disease. (esrf.fr)
- A few months ago, experts were talking about the next generation of "disease-modifying" drugs that were expected to help treat Alzheimer's disease by attacking amyloid plaque in the brain. (ohsu.edu)
- Amyloid" is the stuff that gets in the brain in Alzheimer's disease. (ohsu.edu)
- The theory is that amyloid is toxic to the brain, setting up the slow burn we know as Alzheimer's disease. (ohsu.edu)
- Thus, PrP C is a mediator of amyloid-β-oligomer-induced synaptic dysfunction, and PrP C -specific pharmaceuticals may have therapeutic potential for Alzheimer's disease. (nature.com)
- SAN DIEGO, Calif, January 8, 2016 -- Investigators here have discovered that high sugar caused by Type 2 (adult-onset) diabetes and the beta-amyloid protein associated with Alzheimer's disease induce the same pathological modification on multiple enzymes in the brain. (thefreedictionary.com)
- Beta-amyloid protein is the primary material found in the sticky brain "plaques" characteristic of Alzheimer's disease. (thefreedictionary.com)
- Professor Martins is credited, in collaboration with Australian and German scientists, with isolating beta-amyloid protein , which forms amyloid plaque deposits in the brain, a characteristic diagnostic feature of Alzheimer's disease. (thefreedictionary.com)
- Anti-amyloid drugs are considered "disease-modifying"-that is, they aim to fundamentally change the course of Alzheimer's disease. (xconomy.com)
- The A4 study is a Phase III clinical trial for cognitively normal older adults whose brain scans show evidence of amyloid buildup, which places them at risk for memory loss and cognitive decline associated with Alzheimer's disease. (nih.gov)
- April 30, 2018 -- The presence of amyloid on PET scans may be a sign that adults with no symptoms of dementia are still at risk of mild cognitive impairment or even Alzheimer's disease in the future as they age, according to a study published online April 30 in JAMA Neurology . (auntminnie.com)
- There has been increasing evidence that elevated levels of amyloid in the brain are associated with an increased risk of Alzheimer's disease and could be the first preclinical sign of the illness. (auntminnie.com)
- Beta-amyloid (A beta) plays a key role in the pathogenesis of Alzheimer's disease (AD) by inducing neurotoxicity and cell death mainly through production of reactive oxygen species (ROS). (wellnessresources.com)
- Newswise - MINNEAPOLIS - The scientific community has long believed that beta-amyloid, a protein that can clump together and form sticky plaques in the brain, is the first sign of Alzheimer's disease. (newswise.com)
- Much of the research exploring possible treatments for Alzheimer's disease has focused on targeting amyloid. (newswise.com)
- UCLA scientists and colleagues from UC Riverside and the Human BioMolecular Research Institute have found that a form of vitamin D, together with a chemical found in turmeric spice called curcumin, may help stimulate the immune system to clear the brain of amyloid beta, which forms the plaques considered the hallmark of Alzheimer's disease. (emaxhealth.com)
- The early research findings, which appear in the July issue of the Journal of Alzheimer's Disease, may lead to new approaches in preventing and treating Alzheimer's by utilizing the property of vitamin D3 - a form of vitamin D - both alone and together with natural or synthetic curcumin to boost the immune system in protecting the brain against amyloid beta. (emaxhealth.com)
- BACE1 finding reverses the formation of amyloid plaques in the mice who have Alzheimer's disease, opening a wide door for finding treatment for humans. (emaxhealth.com)
- The presence of beta-amyloid plaque in certain brain regions is one of the telltale signs that a person might develop dementia or Alzheimer's disease. (auntminnie.com)
- Genes that can cause neurofibrillary tangles and amyloid plaques are strongly associated with Alzheimer's disease. (dnalc.org)
- The scans showed that those who had more semantic intrusions on the word test also had higher levels of the protein beta-amyloid that is associated with increased risk of mild cognitive impairment and developing Alzheimer's disease. (nih.gov)
- Given the ability of amyloid fibrils to cross-seed the formation of chemically heterologous fibrils, the speculative etiologic role of dietary amyloid in other disease processes involving amyloid formation such as Alzheimer's disease and Type II Diabetes is also discussed. (environmental-expert.com)
- Accumulating amyloid protein occurred faster among persons deemed to have 'objectively-defined subtle cognitive difficulties' than among persons considered to be 'cognitively normal,' offering potential new early biomarker for Alzheimer's disease. (ucsd.edu)
- The scientific community has long thought that amyloid drives the neurodegeneration and cognitive impairment associated with Alzheimer's disease,' said senior author Mark W. Bondi, PhD, professor of psychiatry at UC San Diego School of Medicine and VASDSH. (ucsd.edu)
Scientists8
- Because of its antioxidant properties, scientists at McGill University in Quebec have demonstrated (in tissue culture) that one form of gingko biloba can prevent the oxidative damage by beta amyloid. (selfgrowth.com)
- In their previous laboratory work scientists were able to show that specific types of immune cells in Alzheimer's patients responded to therapy with vitamin D3 and curcumin, a chemical found in the spice known as turmeric to awaken the patient s own immune system to clear amyloid beta. (bellaonline.com)
- Amyloid PET technology has made it easier for neurologists to diagnose difficult cases of dementia, and also has helped scientists understand how amyloid plaques accumulate during the disease process. (dana.org)
- Encouraged by the amyloid imaging breakthrough, scientists around the world are now racing to develop them. (dana.org)
- So the scientists of the world attacked amyloid with a vengeance, generating drugs to clamp down on the enzyme that produces it, on the process that causes it to crystallize in the brain, and developing synthetic antibodies designed to find and remove it like heat-seeking missiles. (ohsu.edu)
- In both studies, scientists looked for signs of beta-amyloid protein , which forms clumps in the brains of Alzheimer's patients and is a key hallmark of the disease. (thefreedictionary.com)
- However, scientists have evidence that the amyloid-forming protein is expressed more in melanoma cells than in healthy skin. (scienceblog.com)
- Using blood samples from nine Alzheimer's patients, one patient with mild cognitive impairment and three healthy control subjects, scientists isolated monocyte cells, which transform into macrophages that act as the immune system's clean-up crew, traveling through the brain and body and gobbling up waste products, including amyloid beta. (emaxhealth.com)
Brains7
- Amyloid plaques are tell-tale protein deposits found abundantly in the brains of Alzheimer's patients. (eurekalert.org)
- A big boost to Alzheimer's research in recent years has come from the invention of new tracer compounds for mapping amyloid beta plaques in the brains of living people. (dana.org)
- Tau and amyloid tracers label distinct regions of Alzheimer's patients brains [Image courtesy of Neuron, Maruyama et al. (dana.org)
- And this past August, they reported that the drugs did indeed lower the amounts of amyloid in the brains of living patients. (ohsu.edu)
- Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. (nature.com)
- This study will test whether an investigational drug, solanezumab, can slow the progression of memory problems associated with amyloid, a protein that forms plaques in the brains of people with Alzheimer disease. (nih.gov)
- Can Amyloid Spread Between Brains? (the-scientist.com)
Clumps3
- clumps of amyloid-β, known as plaques, that form outside cells, and strings of a protein called tau, known as neurofibrillary tangles, that form inside cells. (nature.com)
- These aggregated proteins form protein clumps called amyloid deposits that accumulate in certain areas of the brain and in its blood vessels . (medlineplus.gov)
- People who suffer from Alzheimer's more often have high levels of beta amyloid which collect in clumps, called senile plaques in the brain. (selfgrowth.com)
Dementia18
- Hereditary cerebral amyloid angiopathy is a condition that can cause a progressive loss of intellectual function (dementia), stroke, and other neurological problems starting in mid-adulthood. (medlineplus.gov)
- People with the Flemish and Italian types of hereditary cerebral amyloid angiopathy are prone to recurrent strokes and dementia. (medlineplus.gov)
- The first sign of the Icelandic type of hereditary cerebral amyloid angiopathy is typically a stroke followed by dementia. (medlineplus.gov)
- Strokes are rare in people with the Arctic type of hereditary cerebral amyloid angiopathy, in which the first sign is usually memory loss that then progresses to severe dementia. (medlineplus.gov)
- Two types of hereditary cerebral amyloid angiopathy, known as familial British dementia and familial Danish dementia, are characterized by dementia and movement problems. (medlineplus.gov)
- The drugmakers themselves have said that in 81 percent of the group taking the highest dose of BAN2401, the amount of amyloid plaque eliminated was enough to take early-stage Alzheimer's patients to a level below what would indicate dementia . (aarp.org)
- The grant award for over $1,500,000 will continue to fund the development of a novel ophthalmic diagnostic compound for Cerebral Amyloid Angiopathy (CAA), an age-associated disease in which proteins called amyloid build up on the walls of the arteries in the brain increasing the risk for stroke caused by bleeding , and dementia . (globenewswire.com)
- When better drugs become available, "amyloid imaging" could enable people to begin therapy in time to avoid or greatly delay Alzheimer's dementia. (dana.org)
- A lot of elderly people show a high density of plaques on amyloid PET scans but don't develop dementia," says Neil Vasdev of Harvard Medical School. (dana.org)
- In another case, an unexpectedly low level of tau labeling in one dementia patient led to the discovery that the man lacked signs of amyloid plaques too, and thus had likely been misdiagnosed with Alzheimer's. (dana.org)
- Aducanumab, an antibody, clears away sticky beta-amyloid protein deposits in the brain that are linked to dementia. (thefreedictionary.com)
- In Parkinson's disease, α-synuclein forms amyloid deposits that are thought to kill dopamine-producing neurons in the brain, causing symptoms such as tremor, slow movements and dementia. (scienceblog.com)
- The same amyloid benchmark has been used to evaluate the risk of looming cognitive impairment and/or dementia in people with no signs of dementia. (auntminnie.com)
- Despite this, there are relatively few population-based estimates of amyloid positivity in the population without dementia," the authors noted. (auntminnie.com)
- Our first objective was therefore to estimate the prevalence of amyloid positivity in a population without dementia. (auntminnie.com)
- A total of 1,671 participants (mean age, 71.3 ± 9.8 years) without dementia underwent amyloid PiB-PET imaging between August 2008 and September 2017. (auntminnie.com)
- Despite the nonsignificant associations by sex for incident Alzheimer's dementia, the higher prevalence of amyloid positivity in women and sex differences in risk of progression for amyloid-positive individuals who are either cognitively unimpaired or have mild cognitive impairment may have implications for reporting clinical trial results by sex," the authors wrote. (auntminnie.com)
- The build-up of beta amyloid plaques is widely believed to cause irreversible brain damage, resulting in a host of cognitive and motor impairments broadly associated with AD, which accounts for about 60 to 80 percent of all cases of dementia in the United States. (ucsd.edu)
Detection of amyloid plaques1
- It uses PET ligands that allow in vivo detection of amyloid plaques, a core pathologic feature of Alzheimer disease (positive amyloid-β [Aβ] status). (cmaj.ca)
Evidence of amyloid deposits2
- The second, A4 (Anti-Amyloid Treatment in Asymptomatic Alzheimer's) is a solanezumab trial sponsored by Lilly that's investigating whether the drug can slow the onset of symptoms in people who have evidence of amyloid deposits in their brain. (forbes.com)
- A confirmed diagnosis of CAA can only be made on the basis of biopsy or autopsy evidence of amyloid deposits in the cerebral blood vessels. (aerzteblatt.de)
Brain29
- It was initially described in 1907 by Dr. Alois Alzheimer when he noticed amyloid plaques in the brain of Auguste Deter, a patient with several cognitive impairment. (news-medical.net)
- The latest study of a drug designed to clear amyloid deposits in the brain raises questions about whether focusing on the plaque-forming protein makes a difference in treating Alzheimer's. (forbes.com)
- The hope was that if the drug could eliminate soluble amyloid-beta-the protein blamed for the brain plaques that form in patients-Alzheimer's progression might be stopped, or at least slowed significantly. (forbes.com)
- Because we now know that amyloid builds up in the brain 15-20 years before symptoms, the broader scientific community has hypothesized that Alzheimer's may need to be targeted earlier in the disease progression. (forbes.com)
- An early trial of the drug detailed in a 2016 paper in the journal Nature did indicate that in patients with a mild form of Alzheimer's, one month of treatment reduced levels of amyloid-beta in the brain and slowed the rate of cognitive decline . (forbes.com)
- The effect of the buildup of beta amyloid in the brain, caused by a variation of a gene known as CYP46, is memory loss better known as Alzheimer's. (selfgrowth.com)
- Excessive buildup of beta amyloid is also associated with high levels of cholesterol in the brain. (selfgrowth.com)
- Cerebral amyloid angiopathy (CAA) is characterized histopathologically by amyloid fibrils in the small to middle-sized blood vessels usually the arteries of the brain. (aerzteblatt.de)
- Other development programs include the detection of Cerebral Amyloid Angiopathy, Creutzfeldt-Jakob disease, and Traumatic Brain Injury, all of which are associated with the presence of amyloid proteins. (globenewswire.com)
- Abstract DESCRIPTION (provided by applicant): The goal of this research project is to define the structure and radioactive label for ligands that will per-mit quantitative measurement of amyloid sites in living brain by external imaging with positron (PET) or single photon (SPECT) emission tomography. (sbir.gov)
- Designed for use with positron emission tomography (PET) scanners, the new tracers are injected into the bloodstream and cross quickly into the brain, where they preferentially bind to amyloid plaques, and mark them-briefly-with emissions of mild radioactivity. (dana.org)
- One of their better optimized compounds, THK-5105, labels the usual brain regions that are hit by tau pathology, and doesn't label amyloid beta deposits, in Alzheimer's brain slices as well as in living patients. (dana.org)
- This is amazing all by itself when you consider that extracting amyloid from brain tissue at autopsy requires concentrated acid and worse. (ohsu.edu)
- There was less amyloid in the brain, but the brain did not work any better. (ohsu.edu)
- A specific amyloid-β protein assembly in the brain impairs memory. (nature.com)
- All volunteers will undergo a positron emission tomography (PET) scan to be determine their brain amyloid levels. (nih.gov)
- The study will test the safety and efficacy of solanezumab, a monoclonal antibody, to see if it slows memory and cognitive decline and affects the buildup of amyloid plaques, as shown by brain imaging and other biomarkers. (nih.gov)
- What we find, very much to our surprise, is that, of these eight patients, four of them had quite significant and quite severe deposition of Alzheimer's amyloid protein in their brain," Collinge said. (the-scientist.com)
- There is very strong evidence coming from transgenic mice experiments that these things can happen in experimental models," Soto said, noting that his group and others have induced amyloid-β deposition in mice by injecting brain extracts from an AD patient. (the-scientist.com)
- The investigators have preliminary evidence that selective serotonin reuptake inhibitor (SSRI) antidepressants lower the amount of amyloid plaques in the human brain. (clinicaltrials.gov)
- Beta-amyloid then leads to other brain changes including neurodegeneration and eventually to thinking and memory problems. (newswise.com)
- The study suggests that subtle thinking and memory differences may come before, or happen alongside, the development of amyloid plaques that can be detected in the brain. (newswise.com)
- Participants had brain scans at the start of the study to determine levels of amyloid plaques in the brain, and then yearly scans for four years. (newswise.com)
- It is also possible that the earliest stages of amyloid plaques forming in the brain are not detectable with brain scans. (newswise.com)
- Conversely, individuals who were not on vascular medication exhibited greater levels of several vascular risk factors, as well as increased beta-amyloid deposition in the brain. (auntminnie.com)
- A simple and inexpensive word recall test accurately predicted whether people had elevated brain levels of beta-amyloid. (nih.gov)
- The LASSI-L also helped sort out these people from individuals who showed clinical symptoms of mild cognitive impairment but had negative amyloid scans and people who were diagnosed with non-Alzheimer's brain disorders that impacted cognition. (nih.gov)
- The new findings, say authors, suggest that Obj-SCD can be detected during the preclinical state of AD when amyloid plaques are accumulating in the brain, neurodegeneration is just starting, but symptoms of impairment on total scores on thinking and memory tests have not yet been recorded. (ucsd.edu)
- A rendering of amyloid protein plaques accumulating between neurons in the brain. (ucsd.edu)
Levels in cerebrospinal fluid1
- A phase I study showed that MK-8931 reduced beta-amyloid protein levels in cerebrospinal fluid by more than 90% in healthy individuals. (medpagetoday.com)
Mild cognitive4
- Our estimates of progression [from] amyloid-positive, cognitively unimpaired status to amnestic mild cognitive impairment may provide reliable and valid information from a population-based study for estimating the outcome of a successful antiamyloid therapeutic agent on a general North American population," wrote lead author Dr. Rosebud Roberts and colleagues. (auntminnie.com)
- Although we did not find a significant interaction of amyloid positivity with sex, higher rates of progression in amyloid-positive women with mild cognitive impairment compared with men may be partly because of the higher prevalence of amyloid positivity in women. (auntminnie.com)
- The study gave the first evidence that semantic errors on cognitive tests like the LASSI-L were more common in people with mild cognitive impairment who were beta-amyloid positive. (nih.gov)
- Utilizing semantic intrusions to identify amyloid positivity in mild cognitive impairment. (nih.gov)
Plaque4
- Unlike phase one results in December 2017, which showed disappointing results after 12 months, this phase - which lasted 18 months - showed how the drug not only cleared out significant amounts of amyloid plaque (a hallmark of the disease) but also seemed to slow the progression of the disease by 30 percent. (aarp.org)
- The nano-XRF distribution maps show that zinc and copper clearly co-localise with the amyloid deposits, while iron appears to be associated with the plaque border ( Figure 2 ). (esrf.fr)
- As for the different types of amyloid plaque, the concentration of iron was found to be higher in fibrillary plaques than in non-fibrillary ones, whereas the levels of copper and zinc were found to be similar in both types of amyloid deposits. (esrf.fr)
- A third team, from Avid Radiopharmaceuticals-developer of one of the existing amyloid plaque tracers-has described successful early tests of their new tau tracer compounds T807 and T808. (dana.org)
Mutations4
- The mutations favour the production of longer variants of amyloid-β that clump together more readily. (nature.com)
- Mutations in the APP gene are the most common cause of hereditary cerebral amyloid angiopathy. (medlineplus.gov)
- A. Abedini and D. P. Raleigh, "Destabilization of human IAPP amyloid fibrils by proline mutations outside of the putative amyloidogenic domain: is there a critical amyloidogenic domain in human IAPP? (hindawi.com)
- While amyloid-β is not uncommon among the elderly, the patients examined in this study were only 36 to 51 years old when they died, and none had mutations that would predispose them to early-onset AD. (the-scientist.com)
Cerebral8
- There are many different types of hereditary cerebral amyloid angiopathy. (medlineplus.gov)
- The various types of hereditary cerebral amyloid angiopathy are named after the regions where they were first diagnosed. (medlineplus.gov)
- The Dutch type of hereditary cerebral amyloid angiopathy is the most common form. (medlineplus.gov)
- The prevalence of hereditary cerebral amyloid angiopathy is unknown. (medlineplus.gov)
- Lefterov I, Fitz NF, Cronican AA, Fogg A, Lefterov P, Kodali R, Wetzel R, Koldamova R . Apolipoprotein A-I deficiency increases cerebral amyloid angiopathy and cognitive deficits in APP/PS1DeltaE9 mice . (alzforum.org)
- Cerebral amyloid angiopathy (CAA) is a degenerative vasculopathy that is classically associated with lobar intracerebral or sulcal hemorrhage. (aerzteblatt.de)
- This review is based on pertinent publications retrieved by a selective search employing the terms amyloid cerebral angiopathy, stroke, intracerebral bleeding, and acute stroke therapy. (aerzteblatt.de)
- These results suggest that APP23 mice have more neurons until they develop amyloid plaques but then lose neurons in the process of cerebral amyloidogenesis. (gu.se)
Alzheimer3
- Fandrich M, Meinhardt J, Grigorieff N. Structural polymorphism of Alzheimer Abeta and other amyloid fibrils. (medscape.com)
- We are working on building high-resolution predictions for medically relevant amyloids, starting with the Alzheimer\'s-beta fragment (1-40). (bakerlab.org)
- This process, called amyloid formation, is a common pathological feature in diseases such as Alzheimer s, Parkinson s and prion diseases, as well as type II diabetes. (phys.org)
Structures8
- The classic "shoulder-pad" sign denotes end-stage amyloid deposits in the shoulder synovium and periarticular structures, but is rarely seen. (medscape.com)
- These deposits often recruit various sugars and other components such as Serum Amyloid P component, resulting in complex, and sometimes inhomogeneous structures. (wikipedia.org)
- Furthermore, bacteria have mechanisms to produce functional amyloid structures with important roles in bacterial physiology and interaction with host cells. (nih.gov)
- However, recent data show that HD6 can form amyloid structures at the gut mucosa with strong affinity for bacterial surfaces. (nih.gov)
- Eisenberg's earlier work on fibrils led to his discovery of steric zippers, and in new work published August 16, 2009, in Nature Structural & Molecular Biology, he adds more zipper patterns to the catalogue of possible amyloid structures. (emaxhealth.com)
- Why predict amyloid structures? (bakerlab.org)
- Amyloids adopt 'cross-β' structures composed of long, twisted fibrils with β-strands running perpendicular to the fibril axis. (rcsb.org)
- We have discovered that a class of systematically designed natural tri- to hexapeptides with a characteristic sequential motif can simulate the process of fiber assembly and further condensation to amyloid fibrils, probably via unexpected dimeric α-helical intermediate structures. (phys.org)
Clump together1
- Plaques form when protein pieces called beta-amyloid (BAY-tuh AM-uh-loyd) clump together. (alz.org)
Beta amyloid buildup1
- The question is: Do these types of vascular medications really provide a deterrent to beta-amyloid buildup? (auntminnie.com)
Form amyloid fibrils1
- [ 5 ] In humans, about 23 different unrelated proteins are known to form amyloid fibrils in vivo. (medscape.com)
Proteins called amyloid1
- One of these factors is the ordered accumulations of misfolded proteins called amyloid fibrils. (asbmb.org)
Islet amyloid formation2
- The mechanism(s) responsible for islet amyloid formation in type 2 diabetes is still unclear but it appears that an increase in the secretion of IAPP, per se, is not sufficient. (nih.gov)
- Sequence divergence in a specific region of islet amyloid polypeptide (IAPP) explains differences in islet amyloid formation between species," FEBS Letters , vol. 251, no. 1-2, pp. 261-264, 1989. (hindawi.com)
Anti-amyloid strategies2
- And even if the evidence that anti-amyloid strategies may fend off Alzheimer's is strong, actually developing the drugs for that purpose will prove challenging, Murphy predicts. (forbes.com)
- Well, it means either that amyloid is not the problem after all, or it means that anti-amyloid strategies have to be started earlier in the game in order to be clinically useful. (ohsu.edu)
Fibril structure prediction1
- How are the results of the amyloid fibril structure prediction coming? (bakerlab.org)
Pathology4
- To date, 37 human proteins have been found to form amyloid in pathology and be associated with well-defined diseases. (wikipedia.org)
- Amydis, Inc., founded in 2013, is a privately-held company discovering novel small molecule drugs to allow direct visualization of CNS molecular pathology through the retina to detect, monitor, and screen diseases that involve the presence of amyloid proteins. (globenewswire.com)
- It's the first in-human indication of potential transmission of amyloid-β pathology," said Claudio Soto of the University of Texas Health Science Center in Houston who was not involved in the study. (the-scientist.com)
- And while it is atypical to see amyloid-β pathology in people this young, it is not unheard of , Trojanowski added. (the-scientist.com)
Diseases6
- In the human body, amyloids have been linked to the development of various diseases. (wikipedia.org)
- BMC is an international referral center for the diagnosis and treatment of systemic amyloid diseases. (bmc.org)
- SAN DIEGO, Sept. 23, 2019 (GLOBE NEWSWIRE) -- Amydis, Inc., a privately-held pharmaceutical company developing proprietary drugs to detect, monitor, and screen for amyloid-related diseases, announced today that they received a Phase 2A SBIR grant award from the National Institute on Aging of the National Institutes of Health (NIH). (globenewswire.com)
- Amydis has a platform of novel compounds that fluoresce when bound to amyloid-related proteins, thus enabling visual diagnosis of such diseases. (globenewswire.com)
- Most people know that amyloids are involved in diseases, such as Parkinson's and Alzheimer's, but it's less well-known that some amyloids, like Pmel, actually serve a useful function," Lee says. (scienceblog.com)
- [ 2 ] Many classic eponymic diseases were later found to be related to a diverse array of misfolded polypeptides (amyloid) that contain the common beta-pleated sheet architecture. (medscape.com)
Gamma-secretase1
- CTF-beta is broken down by gamma-secretase to yield soluble amyloid-beta and membrane-bound AICD. (ebi.ac.uk)
Scans4
- Current diagnosis of CAA involves expensive imaging tests such as MRI, CT scans, and PET amyloid tests. (globenewswire.com)
- Subjects had their first PET amyloid scans beginning in 2008 with four five-minute exams acquired 40 to 60 minutes after injection of PiB. (auntminnie.com)
- Amyloid positivity was based standardized uptake value ratios (SUVRs) greater than 1.42 on the PET scans. (auntminnie.com)
- February 12, 2020 -- Patients who were on cardiovascular medications like cholesterol-lowering drugs seem to have lower levels of amyloid burden on PET scans, according to a study published February 7 in JAMA Network Open . (auntminnie.com)
Neurodegeneration2
- Instead, anti-amyloid drugs would be effective only if introduced much earlier in the disease process, before plaques have become extensive and before neurodegeneration has really taken hold. (medpagetoday.com)
- I would say that neurodegeneration in Alzheimers mouse models was a beta- amyloid thing! (bio.net)