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)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.Amyloid beta-Protein Precursor: A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.Plaque, Amyloid: Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.Serum Amyloid A Protein: An ACUTE PHASE REACTION protein present in low concentrations in normal sera, but found at higher concentrations in sera of older persons and in patients with AMYLOIDOSIS. It is the circulating precusor of amyloid A protein, which is found deposited in AA type AMYLOID FIBRILS.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).Amyloid Precursor Protein Secretases: Endopeptidases that are specific for AMYLOID PROTEIN PRECURSOR. Three secretase subtypes referred to as alpha, beta, and gamma have been identified based upon the region of amyloid protein precursor they cleave.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.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.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.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)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.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.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.Cognition Disorders: Disturbances in mental processes related to learning, thinking, reasoning, and judgment.Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.Neurofibrils: The delicate interlacing threads, formed by aggregations of neurofilaments and neurotubules, coursing through the CYTOPLASM of the body of a NEURON and extending from one DENDRITE into another or into the AXON.Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury.Dementia, Vascular: An imprecise term referring to dementia associated with CEREBROVASCULAR DISORDERS, including CEREBRAL INFARCTION (single or multiple), and conditions associated with chronic BRAIN ISCHEMIA. Diffuse, cortical, and subcortical subtypes have been described. (From Gerontol Geriatr 1998 Feb;31(1):36-44)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.Serum Amyloid P-Component: Amyloid P component is a small, non-fibrillar glycoprotein found in normal serum and in all amyloid deposits. It has a pentagonal (pentaxin) structure. It is an acute phase protein, modulates immunologic responses, inhibits ELASTASE, and has been suggested as an indicator of LIVER DISEASE.Mild Cognitive Impairment: A prodromal phase of cognitive decline that may precede the emergence of ALZHEIMER DISEASE and other dementias. It may include impairment of cognition, such as impairments in language, visuospatial awareness, ATTENTION and MEMORY.Aspartic Acid Endopeptidases: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.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)Presenilin-2: 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. PSEN2 mutations cause ALZHEIMER DISEASE type 4.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Congo Red: An acid dye used in testing for hydrochloric acid in gastric contents. It is also used histologically to test for AMYLOIDOSIS.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.Aniline CompoundsNeurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Presenilins: Integral membrane proteins and essential components of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. Mutations of presenilins lead to presenile ALZHEIMER DISEASE with onset before age 65 years.Mental Status Schedule: Standardized clinical interview used to assess current psychopathology by scaling patient responses to the questions.ThiazolesMagnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques.Cognition: Intellectual or mental process whereby an organism obtains knowledge.Lewy Body Disease: A neurodegenerative disease characterized by dementia, mild parkinsonism, and fluctuations in attention and alertness. The neuropsychiatric manifestations tend to precede the onset of bradykinesia, MUSCLE RIGIDITY, and other extrapyramidal signs. DELUSIONS and visual HALLUCINATIONS are relatively frequent in this condition. Histologic examination reveals LEWY BODIES in the CEREBRAL CORTEX and BRAIN STEM. SENILE PLAQUES and other pathologic features characteristic of ALZHEIMER DISEASE may also be present. (From Neurology 1997;48:376-380; Neurology 1996;47:1113-1124)Memantine: AMANTADINE derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent.Age of Onset: The age, developmental stage, or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual.Cerebral Cortex: The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.Protease Nexins: Extracellular protease inhibitors that are secreted from FIBROBLASTS. They form a covalent complex with SERINE PROTEASES and can mediate their cellular internalization and degradation.Memory Disorders: Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system.National Institute on Aging (U.S.): Component of the NATIONAL INSTITUTES OF HEALTH. Through basic and clinical biomedical research and training, it conducts and supports research into the nature of the aging process and diseases associated with the later stages of life. The Institute was established in 1974.Brain Chemistry: Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.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.Autopsy: Postmortem examination of the body.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.Substantia Innominata: Tissue in the BASAL FOREBRAIN inferior to the anterior perforated substance, and anterior to the GLOBUS PALLIDUS and ansa lenticularis. It contains the BASAL NUCLEUS OF MEYNERT.Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.Nerve Degeneration: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Amyloidogenic Proteins: Proteins that form the core of amyloid fibrils. For example, the core of amyloid A is formed from amyloid A protein, also known as serum amyloid A protein or SAA protein.Insulysin: An enzyme the catalyzes the degradation of insulin, glucagon and other polypeptides. It is inhibited by bacitracin, chelating agents EDTA and 1,10-phenanthroline, and by thiol-blocking reagents such as N-ethylmaleimide, but not phosphoramidon. (Eur J Biochem 1994;223:1-5) EC 18.104.22.168.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.Clioquinol: A potentially neurotoxic 8-hydroxyquinoline derivative long used as a topical anti-infective, intestinal antiamebic, and vaginal trichomonacide. The oral preparation has been shown to cause subacute myelo-optic neuropathy and has been banned worldwide.Tauopathies: Neurodegenerative disorders involving deposition of abnormal tau protein isoforms (TAU PROTEINS) in neurons and glial cells in the brain. Pathological aggregations of tau proteins are associated with mutation of the tau gene on chromosome 17 in patients with ALZHEIMER DISEASE; DEMENTIA; PARKINSONIAN DISORDERS; progressive supranuclear palsy (SUPRANUCLEAR PALSY, PROGRESSIVE); and corticobasal degeneration.Prodromal Symptoms: Clinical or physiological indicators that precede the onset of disease.Prealbumin: A tetrameric protein, molecular weight between 50,000 and 70,000, consisting of 4 equal chains, and migrating on electrophoresis in 3 fractions more mobile than serum albumin. Its concentration ranges from 7 to 33 per cent in the serum, but levels decrease in liver disease.Down Syndrome: A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)Nerve Tissue ProteinsPhenylcarbamates: Phenyl esters of carbamic acid or of N-substituted carbamic acids. Structures are similar to PHENYLUREA COMPOUNDS with a carbamate in place of the urea.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Lewy Bodies: Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of Lewy bodies is the histological marker of the degenerative changes in LEWY BODY DISEASE and PARKINSON DISEASE but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex.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.Nootropic Agents: Drugs used to specifically facilitate learning or memory, particularly to prevent the cognitive deficits associated with dementias. These drugs act by a variety of mechanisms. While no potent nootropic drugs have yet been accepted for general use, several are being actively investigated.Indans: Aryl CYCLOPENTANES that are a reduced (protonated) form of INDENES.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Apolipoprotein E3: A 34-kDa glycosylated protein. A major and most common isoform of apolipoprotein E. Therefore, it is also known as apolipoprotein E (ApoE). In human, Apo E3 is a 299-amino acid protein with a cysteine at the 112 and an arginine at the 158 position. It is involved with the transport of TRIGLYCERIDES; PHOSPHOLIPIDS; CHOLESTEROL; and CHOLESTERYL ESTERS in and out of the cells.Protein Multimerization: The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.Neuropil Threads: Abnormal structures located chiefly in distal dendrites and, along with NEUROFIBRILLARY TANGLES and SENILE PLAQUES, constitute the three morphological hallmarks of ALZHEIMER DISEASE. Neuropil threads are made up of straight and paired helical filaments which consist of abnormally phosphorylated microtubule-associated tau proteins. It has been suggested that the threads have a major role in the cognitive impairment seen in Alzheimer disease.Amnesia: Pathologic partial or complete loss of the ability to recall past experiences (AMNESIA, RETROGRADE) or to form new memories (AMNESIA, ANTEROGRADE). This condition may be of organic or psychologic origin. Organic forms of amnesia are usually associated with dysfunction of the DIENCEPHALON or HIPPOCAMPUS. (From Adams et al., Principles of Neurology, 6th ed, pp426-7)Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Frontotemporal Dementia: The most common clinical form of FRONTOTEMPORAL LOBAR DEGENERATION, this dementia presents with personality and behavioral changes often associated with disinhibition, apathy, and lack of insight.Temporal Lobe: Lower lateral part of the cerebral hemisphere responsible for auditory, olfactory, and semantic processing. It is located inferior to the lateral fissure and anterior to the OCCIPITAL LOBE.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Benzothiazoles: Compounds with a benzene ring fused to a thiazole ring.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Psychomotor Agitation: A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions.Alzheimer Vaccines: Vaccines or candidate vaccines used to prevent or treat ALZHEIMER DISEASE.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.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.Parkinson Disease: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)Cerebral Amyloid Angiopathy, Familial: A familial disorder marked by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES.PC12 Cells: A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.Maze Learning: Learning the correct route through a maze to obtain reinforcement. It is used for human or animal populations. (Thesaurus of Psychological Index Terms, 6th ed)Tacrine: A cholinesterase inhibitor that crosses the blood-brain barrier. Tacrine has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders.Monomeric Clathrin Assembly Proteins: A subclass of clathrin assembly proteins that occur as monomers.Chromosomes, Human, Pair 21: A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.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.LDL-Receptor Related Proteins: A family of proteins that share sequence similarity with the low density lipoprotein receptor (RECEPTORS, LDL).Apolipoprotein E2: One of three major isoforms of apolipoprotein E. In humans, Apo E2 differs from APOLIPOPROTEIN E3 at one residue 158 where arginine is replaced by cysteine (R158--C). In contrast to Apo E3, Apo E2 displays extremely low binding affinity for LDL receptors (RECEPTORS, LDL) which mediate the internalization and catabolism of lipoprotein particles in liver cells. ApoE2 allelic homozygosity is associated with HYPERLIPOPROTEINEMIA TYPE III.alpha-Synuclein: A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.Microscopy, Electron, Transmission: Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Galantamine: A benzazepine derived from norbelladine. It is found in GALANTHUS and other AMARYLLIDACEAE. It is a cholinesterase inhibitor that has been used to reverse the muscular effects of GALLAMINE TRIETHIODIDE and TUBOCURARINE and has been studied as a treatment for ALZHEIMER DISEASE and other central nervous system disorders.Astrocytes: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Glycogen Synthase Kinase 3: A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.Solubility: The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Kluver-Bucy Syndrome: A neurobehavioral syndrome associated with bilateral medial temporal lobe dysfunction. Clinical manifestations include oral exploratory behavior; tactile exploratory behavior; hypersexuality; BULIMIA; MEMORY DISORDERS; placidity; and an inability to recognize objects or faces. This disorder may result from a variety of conditions, including CRANIOCEREBRAL TRAUMA; infections; ALZHEIMER DISEASE; PICK DISEASE OF THE BRAIN; and CEREBROVASCULAR DISORDERS.Frontotemporal Lobar Degeneration: Heterogeneous group of neurodegenerative disorders characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Multiple subtypes or forms are recognized based on presence or absence of TAU PROTEIN inclusions. FTLD includes three clinical syndromes: FRONTOTEMPORAL DEMENTIA, semantic dementia, and PRIMARY PROGRESSIVE NONFLUENT APHASIA.Clusterin: A highly conserved heterodimeric glycoprotein that is differentially expressed during many severe physiological disturbance states such as CANCER; APOPTOSIS; and various NEUROLOGICAL DISORDERS. Clusterin is ubiquitously expressed and appears to function as a secreted MOLECULAR CHAPERONE.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.Postmortem Changes: Physiological changes that occur in bodies after death.Cyclin-Dependent Kinase 5: A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.Genetic Testing: Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).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.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.Age Factors: Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time.Mice, Inbred C57BLNerve Fibers, Myelinated: A class of nerve fibers as defined by their structure, specifically the nerve sheath arrangement. The AXONS of the myelinated nerve fibers are completely encased in a MYELIN SHEATH. They are fibers of relatively large and varied diameters. Their NEURAL CONDUCTION rates are faster than those of the unmyelinated nerve fibers (NERVE FIBERS, UNMYELINATED). Myelinated nerve fibers are present in somatic and autonomic nerves.Entorhinal Cortex: Cerebral cortex region on the medial aspect of the PARAHIPPOCAMPAL GYRUS, immediately caudal to the OLFACTORY CORTEX of the uncus. The entorhinal cortex is the origin of the major neural fiber system afferent to the HIPPOCAMPAL FORMATION, the so-called PERFORANT PATHWAY.Proteolysis: Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Neurocalcin: A neuronal calcium sensor protein that is expressed as several isoforms and can interact with ACTIN; TUBULIN; and CLATHRIN.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Frontal Lobe: The part of the cerebral hemisphere anterior to the central sulcus, and anterior and superior to the lateral sulcus.Severity of Illness Index: Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder.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.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).Image Processing, Computer-Assisted: A technique of inputting two-dimensional images into a computer and then enhancing or analyzing the imagery into a form that is more useful to the human observer.CA2 Region, Hippocampal: A subsection of the hippocampus, described by Lorente de No, that is located between the HIPPOCAMPUS CA1 FIELD and the HIPPOCAMPUS CA3 FIELD.Cell Line: Established cell cultures that have the potential to propagate indefinitely.PrPC Proteins: Normal cellular isoform of prion proteins (PRIONS) encoded by a chromosomal gene and found in normal and scrapie-infected brain tissue, and other normal tissue. PrPC are protease-sensitive proteins whose function is unknown. Posttranslational modification of PrPC into PrPSC leads to infectivity.Caregivers: Persons who provide care to those who need supervision or assistance in illness or disability. They may provide the care in the home, in a hospital, or in an institution. Although caregivers include trained medical, nursing, and other health personnel, the concept also refers to parents, spouses, or other family members, friends, members of the clergy, teachers, social workers, fellow patients.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.Protein PrecursorsPsychiatric Status Rating Scales: Standardized procedures utilizing rating scales or interview schedules carried out by health personnel for evaluating the degree of mental illness.Caspase 6: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 7; CASPASE 8; and CASPASE 10. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Dominican Republic: A republic in the Greater Antilles in the West Indies. Its capital is Santo Domingo. With Haiti, it forms the island of Hispaniola - the Dominican Republic occupying the eastern two thirds, and Haiti, the western third. It was created in 1844 after a revolt against the rule of President Boyer over the entire island of Hispaniola, itself visited by Columbus in 1492 and settled the next year. Except for a brief period of annexation to Spain (1861-65), it has been independent, though closely associated with the United States. Its name comes from the Spanish Santo Domingo, Holy Sunday, with reference to its discovery on a Sunday. (From Webster's New Geographical Dictionary, 1988, p338, 506 & Room, Brewer's Dictionary of Names, 1992, p151)Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Circular Dichroism: A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98.Microtubule-Associated Proteins: High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Amyloidosis, Familial: Diseases in which there is a familial pattern of AMYLOIDOSIS.Fluorodeoxyglucose F18: The compound is given by intravenous injection to do POSITRON-EMISSION TOMOGRAPHY for the assessment of cerebral and myocardial glucose metabolism in various physiological or pathological states including stroke and myocardial ischemia. It is also employed for the detection of malignant tumors including those of the brain, liver, and thyroid gland. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1162)Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Caribbean Region: The area that lies between continental North and South America and comprises the Caribbean Sea, the West Indies, and the adjacent mainland regions of southern Mexico, Central America, Colombia, and Venezuela.Blood-Brain Barrier: Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.Neurites: In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Neurofilament Proteins: Type III intermediate filament proteins that assemble into neurofilaments, the major cytoskeletal element in nerve axons and dendrites. They consist of three distinct polypeptides, the neurofilament triplet. Types I, II, and IV intermediate filament proteins form other cytoskeletal elements such as keratins and lamins. It appears that the metabolism of neurofilaments is disturbed in Alzheimer's disease, as indicated by the presence of neurofilament epitopes in the neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit of the neurofilament triplet in brains of Alzheimer's patients. (Can J Neurol Sci 1990 Aug;17(3):302)Predictive Value of Tests: In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Family Health: The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).Cerebral Ventricles: Four CSF-filled (see CEREBROSPINAL FLUID) cavities within the cerebral hemispheres (LATERAL VENTRICLES), in the midline (THIRD VENTRICLE) and within the PONS and MEDULLA OBLONGATA (FOURTH VENTRICLE).Aphasia, Primary Progressive: A progressive form of dementia characterized by the global loss of language abilities and initial preservation of other cognitive functions. Fluent and nonfluent subtypes have been described. Eventually a pattern of global cognitive dysfunction, similar to ALZHEIMER DISEASE, emerges. Pathologically, there are no Alzheimer or PICK DISEASE like changes, however, spongiform changes of cortical layers II and III are present in the TEMPORAL LOBE and FRONTAL LOBE. (From Brain 1998 Jan;121(Pt 1):115-26)Lemur: A genus of the family Lemuridae consisting of five species: L. catta (ring-tailed lemur), L. fulvus, L. macaco (acoumba or black lemur), L. mongoz (mongoose lemur), and L. variegatus (white lemur). Most members of this genus occur in forested areas on Madagascar and the Comoro Islands.Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Meninges: The three membranes that cover the BRAIN and the SPINAL CORD. They are the dura mater, the arachnoid, and the pia mater.Ethylene Glycols: An ethylene compound with two hydroxy groups (-OH) located on adjacent carbons. They are viscous and colorless liquids. Some are used as anesthetics or hypnotics. However, the class is best known for their use as a coolant or antifreeze.Synucleins: A family of homologous proteins of low MOLECULAR WEIGHT that are predominately expressed in the BRAIN and that have been implicated in a variety of human diseases. They were originally isolated from CHOLINERGIC FIBERS of TORPEDO.Kinetics: The rate dynamics in chemical or physical systems.Lysosomes: A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Copper: A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of ACETYLCHOLINE to CHOLINE and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 22.214.171.124.Cricetulus: A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Genome-Wide Association Study: An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.Parahippocampal Gyrus: A convolution on the inferior surface of each cerebral hemisphere, lying between the hippocampal and collateral sulci.Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.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)Immunotherapy, Active: Active immunization where vaccine is administered for therapeutic or preventive purposes. This can include administration of immunopotentiating agents such as BCG vaccine and Corynebacterium parvum as well as biological response modifiers such as interferons, interleukins, and colony-stimulating factors in order to directly stimulate the immune system.Encephalitis: Inflammation of the BRAIN due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see ENCEPHALITIS, VIRAL) are a relatively frequent cause of this condition.Cerebrovascular Circulation: The circulation of blood through the BLOOD VESSELS of the BRAIN.Hydrocephalus, Normal Pressure: A form of compensated hydrocephalus characterized clinically by a slowly progressive gait disorder (see GAIT DISORDERS, NEUROLOGIC), progressive intellectual decline, and URINARY INCONTINENCE. Spinal fluid pressure tends to be in the high normal range. This condition may result from processes which interfere with the absorption of CSF including SUBARACHNOID HEMORRHAGE, chronic MENINGITIS, and other conditions. (From Adams et al., Principles of Neurology, 6th ed, pp631-3)Glial Fibrillary Acidic Protein: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000.Early Diagnosis: Methods to determine in patients the nature of a disease or disorder at its early stage of progression. Generally, early diagnosis improves PROGNOSIS and TREATMENT OUTCOME.
Kerr ML, Small DH (Apr 2005). "Cytoplasmic domain of the beta-amyloid protein precursor of Alzheimer's disease: function, ... Wang DS, Dickson DW, Malter JS (2006). "beta-Amyloid degradation and Alzheimer's disease". Journal of Biomedicine & ... a peptide implicated in the pathogenesis of Alzheimer's disease. The underlying cause or causes of the disease are unclear, ... Numerous in vitro and in vivo studies have shown correlations between IDE, Aβ degradation, and Alzheimer's disease. Mice ...
Beyreuther K, Masters CL (Oct 1997). "Alzheimer's disease. The ins and outs of amyloid-beta". Nature. 389 (6652): 677-8. doi: ... hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in Alzheimer's disease". ... hydroxyacyl-coenzyme A dehydrogenase is identical to an amyloid beta-peptide-binding protein involved in Alzheimer's disease". ... "An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease". Nature. 389 (6652 ...
Yoo, Ki-Yeol; Park, So-Young (2012). "Terpenoids as Potential Anti-Alzheimer's Disease Therapeutics". Molecules. 17 (12): 3524- ... Tenuifolins inhibit beta-amyloid synthesis in vitro. Tenuifolins have nootropic activity in vivo via acetylcholine esterase ... inhibits amyloid-β secretionin vitro". Acta Physiologica. 196 (4): 419-25. doi:10.1111/j.1748-1716.2009.01961.x. PMID 19208093 ...
Iwata N, Higuchi M, Saido TC (November 2005). "Metabolism of amyloid-beta peptide and Alzheimer's disease". Pharmacol. Ther. ... Hama E, Saido TC (2005). "Etiology of sporadic Alzheimer's disease: somatostatin, neprilysin, and amyloid beta peptide". Med. ... Wang DS, Iwata N, Hama E, Saido TC, Dickson DW (October 2003). "Oxidized neprilysin in aging and Alzheimer's disease brains". ... Neprilysin-deficient knockout mice show both Alzheimer's-like behavioral impairment and amyloid-beta deposition in the brain, ...
Pittsburgh compound B
Furthermore, as novel disease-modifying therapies for Alzheimer's disease that attack and remove beta-amyloid deposits from the ... The definitive diagnosis of Alzheimer's disease can only be made following the demonstration of the presence of beta-amyloid ... Florbetapir Florbetaben Flutemetamol List of PET radiotracers Klunk, W.E., et al., Imaging brain amyloid in Alzheimer's disease ... doi:10.1016/s0024-3205(01)01232-2. Herholz, K; Ebmeier, K (2011). "Clinical Amyloid Imaging in Alzheimer's Disease". Lancet ...
"New class of inhibitors of amyloid-beta fibril formation. Implications for the mechanism of pathogenesis in Alzheimer's disease ... Callaway's laboratory discovered potential therapeutics for Alzheimer's disease based upon apomorphine., after an earlier paper ... "A molecular model of Alzheimer amyloid ß-peptide fibril formation". J Biol Chem. 274 (18): 12619-12625. doi:10.1074/jbc.274.18. ... of his developed models of Alzheimer amyloid formation. He has also initiated the study of protein domain dynamics by neutron ...
"Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides". J. Biol. Chem. 280 (45): 37377-82. doi:10.1074/ ... in reducing the risk factors associated with Alzheimer's disease. The study showed that resveratrol found in Cabernet Sauvignon ... can reduce levels of amyloid beta peptides, which attack brain cells and are part of the etiology of Alzheimer's. Resveratrol ... In general, Cabernet Sauvignon has good resistance to most grape diseases, powdery mildew being the most noted exception. It is ...
... fiber formation and a potential therapeutic for Alzheimer's disease (AD) under the amyloid hypothesis. Apomorphine and its ... Implications for the mechanism of pathogenesis in Alzheimer's disease". J Biol Chem. 277 (45): 42881-42890. doi:10.1074/jbc. ... Apomorphine is useful in diseases where dopamine levels are lower than normal, such as Parkinson's disease, and can help to ... "Apomorphine treatment in Alzheimer mice promoting amyloid-β degradation". Ann Neurol. 69 (2): 248-56. doi:10.1002/ana.22319. ...
"RAGE and Amyloid-β Peptide Neurotoxicity in Alzheimer's Disease". Nature. 382 (6593): 685-91. doi:10.1038/382685a0. Yang, X ( ... and have been shown to correlate with Alzheimer's Disease, implicating it as a neurotoxic causative compound of the disease. ... Walton, J (2006). "Aluminum in Hippocampal Neurons from Humans with Alzheimer's Disease". NeuroToxicology. 27 (3): 385-94. doi: ... Relevance to Alzheimer Disease". Proceedings of the National Academy of Sciences. 91 (8): 3270-274. doi:10.1073/pnas.91.8.3270 ...
"Animal models of amyloid-beta-related pathologies in Alzheimer's disease". The FEBS Journal. 277 (6): 1389-409. doi:10.1111/j. ... associated with increased β-amyloid deposition (a core feature of Alzheimer's disease progression). CC chemokine receptors ... previously associated with Alzheimer's disease), but also because CCL2 is expressed at high concentrations in macrophages found ... "Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease". Nature Medicine. 13 (4 ...
An important part of the disease process in Alzheimer's disease is the accumulation of Amyloid beta (Aβ) protein. To form Aβ, ... "Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and ... The lengths associated with Alzheimer's disease are 40 and 42 amino acids long. Aβ 42 is more likely to aggregate to form ... They were first identified in screens for mutations causing early onset forms of familial Alzheimer's Disease by Peter St ...
This gene is a candidate gene for Alzheimer's disease. APBA3 has been shown to interact with Amyloid precursor protein. GRCh38 ... It is an adapter protein that interacts with the Alzheimer's disease amyloid precursor protein. This gene product is believed ... Morishima-Kawashima M, Ihara Y (2002). "[Recent advances in Alzheimer's disease]". Seikagaku. 73 (11): 1297-307. PMID 11831025 ... interacts with Alzheimer's beta-amyloid precursor protein". Biochem Biophys Res Commun. 255 (3): 663-7. doi:10.1006/bbrc. ...
Tanzi, RE.; Bertram, L. (February 2005). "Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective". ... In fact, protein aggregates have been implicated in a wide variety of disease known as amyloidoses, including ALS, Alzheimer's ... July 2004). "Formation of amyloid aggregates from human lysozyme and its disease-associated variants using hydrostatic pressure ... September 2001). "The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation". Nat ...
... and Amyloid β containing pyroglutamic acid is increased in Alzheimer's disease and may be involved in the disease process. ... a hatchet man in Alzheimer disease". J Biol Chem. 286 (45): 38825-32. doi:10.1074/jbc.R111.288308. PMID 21965666. Liss, DB; ... doi:10.1016/0278-5846(89)90112-7. Jawhar, S; Wirths, O; Bayer, TA (November 11, 2011). "Pyroglutamate amyloid-β (Aβ): ...
Alleviates Amyloid-β Induced Toxicity in Rat Primary Hippocampal Cultures". Journal of Alzheimer's Disease. 20 (2): 423-426. ... in the treatment of Alzheimer's disease". Journal of Alzheimer's disease : JAD. 6 (1): 17-26. PMID 15004324. Froud, Kristina E ... Alleviates Amyloid-β Induced Toxicity in Rat Primary Hippocampal Cultures". Journal of Alzheimer's Disease. 20 (2): 423-426. ... Significant research has been done on Colostrinin's possible efficacy in Alzheimer's disease, the most common form of dementia ...
Collagen, type XXV, alpha 1
2005). "Characterization of the Alzheimer's disease-associated CLAC protein and identification of an amyloid beta-peptide- ... 2004). "Molecular identification of AMY, an Alzheimer disease amyloid-associated protein". J. Neuropathol. Exp. Neurol. 62 (11 ... 2005). "Collagenous Alzheimer amyloid plaque component assembles amyloid fibrils into protease resistant aggregates". FEBS J. ... a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC-P/collagen type XXV". EMBO J. 21 (7): ...
Amyloid-β peptides are one of the hallmarks of Alzheimer's disease. When they are not degraded properly, these peptides ... Since subjects with Alzheimer's disease have lower sulfatide levels, the clearance of amyloid-β peptides is lower, which allows ... In Alzheimer's disease, sulfatide in the brain tissue decreases tremendously, starting in the early stages of the disease. In ... When comparing sulfatide depletion to other neurodegenerative diseases, Alzheimer's disease is the only case in which sulfatide ...
"Alzheimer's disease beta-amyloid peptides are released in association with exosomes". Proceedings of the National Academy of ... He was interested also in the role of lipids and protein sorting in neurodegenerative diseases, especially in Alzheimer's ... "Efficient inhibition of the Alzheimer's disease beta-secretase by membrane targeting". Science. 320 (5875): 520-523. doi: ... the disease common in the eastern Finland where eating raw fish is popular. After completing his PhD in medicine in 1964, he ...
... in Alzheimer's disease are amyloid-beta and tau, in Parkinson's disease is alpha-synuclein and in Huntington's disease is ... beta amyloid: the major component of senile plaques in Alzheimer's disease. prion: main component of prion diseases and ... Alzheimer's disease, Parkinson's disease and in Huntington's disease the expression of the transglutaminase enzyme is increased ... Alzheimer's disease has been hypothesized to be a protein misfolding disease (proteopathy), caused by accumulation of ...
December 2007). "Cystatin C inhibits amyloid-beta deposition in Alzheimer's disease mouse models". Nat. Genet. 39 (12): 1440- ... It also seems to play a role in brain disorders involving amyloid (a specific type of protein deposition), such as Alzheimer's ... Cystatin C levels have been reported to be higher in subjects with Alzheimer's disease. The role of cystatin C in multiple ... Since cystatin 3 also binds amyloid β and reduces its aggregation and deposition, it is a potential target in Alzheimer's ...
Positron emission tomography-magnetic resonance imaging
Additionally, variations in the locational characteristics of β-amyloid precursor proteins seen in Alzheimer's disease are ... There are a larger number of Hb's found in people with Alzheimer's disease than those without the disease. Additionally many ... "Macroautophagy-a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease". J Cell Biol. 171 (1): 87-98. doi ... such as Alzheimer's disease and Creutzfeldt-Jakob disease. Hirano bodies were first described in the CA1 in patients with ...
... from amyloid precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease. ... Phiel CJ, Wilson CA, Lee VM, Klein PS (May 2003). "GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides ... Selkoe DJ (1994). "Cell biology of the amyloid beta-protein precursor and the mechanism of Alzheimer's disease". Annu. Rev. ... Alzheimer's disease (AD) patients with an inherited form of the disease may carry mutations in the presenilin proteins (PSEN1; ...
Finally, Villa-Komaroff contributed to the discovery that a molecule known to be associated with Alzheimer's disease (amyloid ... and helped stimulate a very large field dedicated to preventing and treating Alzheimer's disease by targeting amyloid beta. ... "Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease". Science. 245: 417-420. doi:10.1126/ ... Before this publication, it was unclear whether amyloid beta was a byproduct of neuronal degeneration or a contributor to that ...
Phiel CJ, Wilson CA, Lee VM, Klein PS (2003). "GSK-3α regulates production of Alzheimer's disease amyloid-β peptides". Nature. ... Brewer GJ (2015). "Divalent copper as a major triggering agent in Alzheimer's Disease". Journal of Alzheimer's Disease. 46 (3 ... "Disturbed copper bioavailability in Alzheimer's Disease". International Journal of Alzheimer's Disease. 2011: 1-5. doi:10.4061/ ... "Deficiency of the copper chaperone for superoxide dismutase increases amyloid-β production". Journal of Alzheimer's Disease. 21 ...
Prevention of dementia
Alzheimer's disease causes inflammation in the neurons by its deposits of amyloid beta peptides and neurofibrillary tangles. ... Alzheimer's Disease Tomorrow?". WebMD. Retrieved 21 March 2016. Eileen M., Welsh (2003). "Focus on Alzheimer's disease research ... This leads to less formation of amyloid plaques seen in Alzheimer's disease. Estrogen may also help in the prevention of ... after Alzheimer's disease), reducing the risk of cerebrovascular disease also reduces the risk of dementia. Thus, physical ...
Christine Van Broeckhoven
"For the genetic investigation of Alzheimer's disease and other neurodegenerative diseases". She was the winner of the European ... Amyloid beta protein precursor gene and hereditary cerebral hemorrhage with amyloidosis, Science. 1990 June 1;248(4959):1120-2 ... 1992 Dec;2(4):335-9. Van Broeckhoven C., Presenilins and Alzheimer disease, Nat Genet. 1995 Nov;11(3):230-2. Genes, Brain and ... early Alzheimer's disease. In 2005, she was awarded the Arkprijs van het Vrije Woord. In 2006, she was awarded as laureate for ...
Neurobiological effects of physical exercise
... the cognitive effects of exercise on Alzheimer's disease may result from a reduction in the quantity of amyloid plaque. The ... "Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease". J. Neurosci. 25 (17): 4217-21. doi: ... particularly Alzheimer's disease and Parkinson's disease. Regular exercise is also associated with a lower risk of developing ... "Protective Effects of Physical Exercise in Alzheimer's Disease and Parkinson's Disease: A Narrative Review". J Clin Neurol. 11 ...
"Alzheimer's disease amyloid-beta links lens and brain pathology in Down syndrome". PLoS ONE. 5 (5): e10659. doi:10.1371/journal ... Maes OC, Schipper HM, Chertkow HM, Wang E (June 2009). "Methodology for discovery of Alzheimer's disease blood-based biomarkers ... Male Alzheimer's patients have shown a decrease in expression of C21orf59 in their blood cells. The C21orf59 gene lies within ... It is of interest in part for its association with various diseases. It has been found in high levels in the bone marrow of ...
P-type calcium channel
In Alzheimer Disease, there is a progressive accumulation of β-amyloid protein (Aβ) in brain. Amyloid plaques develop which ... Changing the cellular calcium ion concentration acts as a trigger for multiple diseases, in severe cases these diseases can ... angina pectoris and Alzheimer's disease. Although many of the therapeutic compounds' main target is not P-type channels, ... offering a possible cause for the toxicity in Alzheimer Disease patients. The CACNA1A gene codes for the alpha subunit of the P ...
人類基因組 - 维基百科，自由的百科全
Positron emission tomography
... naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer's disease ... These amyloid imaging probes permit the visualization of amyloid plaques in the brains of Alzheimer's patients and could assist ... March 1999). "In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease". Neurology. 52 (4): ... and also to make early diagnoses of Alzheimer's disease. The advantage of FDG-PET for these uses is its much wider availability ...
Genetically modified tomato
"Transgenic tomatoes expressing human beta-amyloid for use as a vaccine against Alzheimer's disease". Biotechnology letters. 30 ... Korean scientists are looking at using the tomato to express a vaccine against Alzheimer's disease. Hilary Koprowski, who ... of a synthesized gene encoding cationic peptide cecropin B in transgenic tomato plants protects against bacterial diseases". ...
Parkinson's Disease and Alzheimer's Disease. There is also an interest in the military potential of biological neurotoxins ... "Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain". Proceedings of ... "Neurobiology of Disease. 25 (2): 360-366. doi:10.1016/j.nbd.2006.10.002. PMC 3959771. PMID 17098435.. ... Byth S (July 1980). "Palm Island mystery disease". The Medical Journal of Australia. 2 (1): 40, 42. PMID 7432268.. ...
Frackowiak J, Mazur-Kolecka B, Kaczmarski W, Dickson D (2001). "Deposition of Alzheimer's vascular amyloid-beta is associated ... A compound heterozygous mutation of the HADHB gene can causes axonal Charcot-Marie-tooth disease, which is a neurological ... "A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-tooth disease". BMC Medical Genetics. 14: 125. ...
Brain-derived neurotrophic factor
Alzheimer's disease, Huntington's disease, Rett syndrome, and dementia, as well as anorexia nervosa and ... Studies suggest that neurotrophic factors have a protective role against amyloid beta toxicity. ... "BDNF and Alzheimer's Disease - What's the Connection?". Alzforum: Live Discussions. Alzheimer Research Forum. Archived from the ... Alzheimer's disease. Post mortem analysis has shown lowered levels of BDNF in the brain tissues of people with ...
Beta-amiloide, a enciclopedia libre
"The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide". PLoS ONE 5 (3): e9505. Bibcode:2010PLoSO... ... Implications for the role of amyloid-beta 1-42 in Alzheimer's disease". J. Biol. Chem. 271 (50): 32185-91. PMID 8943274. doi: ... Citron M (September 2004). "Strategies for disease modification in Alzheimer's disease". Nat. Rev. Neurosci. 5 (9): 677-85. ... "Amyloid plaque core protein in Alzheimer disease and Down syndrome". Proc. Natl. Acad. Sci. U.S.A. 82 (12): 4245-9. Bibcode: ...
Epigenetics of neurodegenerative diseases
"Neuroglobin attenuates beta-amyloid neurotoxicity in vitro and transgenic Alzheimer phenotype in vivo". primary. Proceedings of ... Alzheimer's Disease (AD). Main article: Alzheimer's Disease. Alzheimer's disease (AD) is the most prevalent form of ... Disease: amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Huntington's disease (HD), spinal muscular atrophy (SMA ... "Dysregulation of histone acetylation in the APP/PS1 mouse model of Alzheimer's disease". Journal of Alzheimer's Disease. 18 (1 ...
Alzheimer's diseaseEdit. PrPC protein is one of several cellular receptors of soluble amyloid beta (Aβ) oligomers, which are ... Laurén J (2014). "Cellular prion protein as a therapeutic target in Alzheimer's disease". Journal of Alzheimer's Disease. 38 (2 ... "Alzheimer's disease and prion protein". Intractable & Rare Diseases Research. 2 (2): 35-44. doi:10.5582/irdr.2013.v2.2.35. PMC ... The decreased risk in V allele carriers is further limited to late-onset Alzheimer's disease only (≥ 65 years). PRNP can ...
"Genetic determinants of disease progression in Alzheimer's disease". Journal of Alzheimer's Disease. 43 (2): 649-55. doi: ... it has been speculated that it may have a role in axonal transport and influence the expression of the amyloid precursor ... Table 1. CASS4 disease association Screen purpose Observation Alzheimer's disease SNP rs7274581 T/C linked to risk.. Odds ratio ... "Alzheimer's disease risk genes and mechanisms of disease pathogenesis". Biological Psychiatry. 77 (1): 43-51. doi:10.1016/j. ...
Strok bahasa Indonesia, ensiklopedia bebas
Demyelinating disease, hipoglisemia, hiperglisemia, primary ocular disease-glaucoma, vitreal hemorrhage. floaters and the like ... Akan tetapi stroke tidak mempengaruhi kadar β-amyloid, ApoE dan klusterin dalam CSF. ... Alzheimer dan schizophrenia. ... but disease is present), 9 bagi grading is not possible due to ... "Cerebrovascular Disease Service, Palmer 127, West Campus, Beth Israel Deaconess Medical Center; Caplan LR. Diakses tanggal 2011 ...
Brain-derived neurotrophic factor
Alzheimer's disease, Huntington's disease, Rett syndrome, and dementia, as well as anorexia nervosa and ... Studies suggest that neurotrophic factors have a protective role against amyloid beta toxicity. ... "BDNF and Alzheimer's Disease - What's the Connection?". Alzforum: Live Discussions. Alzheimer Research Forum. Archived from the ... Alzheimer's disease. Post mortem analysis has shown lowered levels of BDNF in the brain tissues of people with ...
Alzheimer's disease, depression, and other diseases affecting the brain. It has also been used to study the metabolism of other ... Familial amyloid neuropathy. Autoimmune and demyelinating disease. *Guillain-Barré syndrome. *Chronic inflammatory ... A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged. This damage ... Demyelinating diseases are traditionally classified in two kinds: demyelinating myelinoclastic diseases and demyelinating ...
This experiment represents the first in-vivo model of Alzheimer's Disease that features both beta-amyloid plaques and ... Studies on human brain tissue of ALS/PDC, ALS, Alzheimer's disease, Parkinson's disease, Huntington's disease and neurological ... both hallmarks of tangle diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), ... found that vervets orally administered BMAA developed hallmark histopathology features of Alzheimer's Disease including amyloid ...
డౌన్ సిండ్రోమ్ - వికీపీడియా
Weksler, ME; Szabo, P; Relkin, NR; Reidenberg, MM; Weksler, BB; Coppus, AM (Apr 2013). "Alzheimer's disease and Down's syndrome ... డౌన్ సిండ్రోమ్లో సంభవించే చిత్తవైకల్యం మెదడులో ఉత్పత్తి చేయబడిన అమిలోయిడ్ బీటా పెప్టైడ్ ( amyloid beta peptide )కంటే అధికం ... Alzheimer's Disease, and Cancer: A Brief Review and Hypothesis". Brain Sciences. 8 (4): 53. doi:10.3390/brainsci8040053. PMC ... Hammer, edited by Stephen J. McPhee, Gary D. (2010). "Pathophysiology of Selected Genetic Diseases". Pathophysiology of disease ...
Parkinson's disease, Alzheimer's disease and autism spectrum disorders. ... Studies in cells and in mouse have shown that specifically targeting Amyloid beta-producing genes (e.g. BACE1 and APP) by RNAi ... Neurological diseasesEdit. RNAi strategies also show potential for treating neurodegenerative diseases. ... Disease Phase Status Company Identifier ALN-VSP02 KSP and VEGF LNP Solid tumours I Completed Alnylam Pharmaceuticals ...
Latrepirdin - Википедија, слободна енциклопедија
Medivation's Dimebon(TM) Maintains Statistically Significant Benefit on All Five Efficacy Endpoints in Alzheimer's Disease ... Dimebon and tacrine inhibit neurotoxic action of beta-amyloid in culture and block L-type Ca(2+) channels". Bulletin of ... Novel Alzheimer's Drug Flops, MedPage Today, March 03, 2010 *^ Phase III Failure Leads Medivation and Pfizer to Ditch Dimebon ... Wu J, Li Q, Bezprozvanny I (2008). „Evaluation of Dimebon in cellular model of Huntington's disease". Molecular ...
List of vaccine topics
Non-infectious diseases. *Alzheimer's disease amyloid protein vaccine. *Breast cancer vaccine ... Viral diseases. Virus. Diseases or conditions. Vaccine(s). Brands Hepatitis A virus. Hepatitis A. Hepatitis A vaccine. ... Bacterial diseases. Bacterium. Diseases or conditions. Vaccine(s). Brands Bacillus anthracis. Anthrax. Anthrax vaccines. ... "Lyme Disease Vaccine". Lyme Info. Retrieved April 24, 2013.. *^ Bagnoli, F.; Bertholet, S.; Grandi, G. (2012). "Inferring ...
"RAGE and Amyloid-β Peptide Neurotoxicity in Alzheimer's Disease." Nature, 382 (6593): 685-91. ... Walton, J. (2006) "Aluminum in Hippocampal Neurons from Humans with Alzheimer's Disease." NeuroToxicology, 27 (3): 385-94. ... Relevance to Alzheimer Disease." Proceedings of the National Academy of Sciences, 91 (8): 3270-274. ... Lorenzo, A. (1994) " β-Amyloid Neurotoxicity Requires Fibril Formation and Is Inhibited by Congo Red." Proceedings of the ...
Robert J. Cotter
Ugonjwa wa Alzheimer, kamusi elezo huru
Wozniak M, Mee A, Itzhaki R (2008). "Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques". J ... therapy with remberTM arrests disease progression in mild and moderate Alzheimer's disease over 50 weeks". Alzheimer's & ... Hardy J, Allsop D (Oktoba 1991). "Amyloid deposition as the central event in the aetiology of Alzheimer's disease". Trends ... Geula C, Mesulam MM (1995). "Cholinesterases and the pathology of Alzheimer disease". Alzheimer Dis Assoc Disord 9 Suppl 2: 23- ...
... particularly Alzheimer's disease and Parkinson's disease. Regular exercise is also associated with a ... Cognitive decline in AD is attributable at least in part to the buildup of amyloid and tau proteins, which promote neuronal ... "Protective Effects of Physical Exercise in Alzheimer's Disease and Parkinson's Disease: A Narrative Review". J Clin Neurol. 11 ... Alzheimer's disease (AD) is a progressive neurological disorder characterized by loss in cognitive function, abnormal behavior ...
Copper and zinc are known to bind to amyloid beta proteins in Alzheimer's disease. This bound form is thought to mediate the ... Brewer GJ (February 2007). "Iron and copper toxicity in diseases of aging, particularly atherosclerosis and Alzheimer's disease ... Elevated free copper levels exist in Alzheimer's disease, which has been hypothesized to be linked to inorganic copper ... "The risk of copper toxicity contributing to cognitive decline in the aging population and to Alzheimer's disease". J. Am. Coll ...
Positron emission tomography
... naphthylethylidene derivatives as positron emission tomography imaging probes for beta-amyloid plaques in Alzheimer's disease" ... These amyloid imaging probes permit the visualization of amyloid plaques in the brains of Alzheimer's patients and could assist ... In practice, since the brain is normally a rapid user of glucose, and since brain pathologies such as Alzheimer's disease ... March 1999). "In vivo mapping of cerebral acetylcholinesterase activity in aging and Alzheimer's disease". Neurology. 52 (4): ...
Apolipoproteína E, a enciclopedia libre
... high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease". ... "Impact of apolipoprotein E on Alzheimer's disease". Current Alzheimer Research 10 (8): 809-17. PMC 3995977. PMID 23919769. doi: ... and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer ... Ashford JW (2004). "APOE genotype effects on Alzheimer's disease onset and epidemiology". Journal of Molecular Neuroscience 23 ...
2015). "Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer disease: Phase 3 study". Alzheimer's & Dementia. 11 ... Alzheimer's Disease International.. *^ a b Beach, T.G.; et al. (2012). "Accuracy of the Clinical Diagnosis of Alzheimer Disease ... Alzheimer's disease and amyloid-beta PET imaging. 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): ...
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 ... Alzheimers Disease and the Brain. 8 9 10 11 12 13 14 15 16 ... Beta-amyloid comes from a larger protein found in the fatty ... Alzheimers Association National Office, 225 N. Michigan Ave., Fl. 17, Chicago, IL 60601. Alzheimers Association is a not-for- ...
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 ... The researchers used normal mice, a mouse model of Alzheimers disease, and human cells to study copper-induced amyloid-beta ... leading to amyloid-beta plaques that are the hallmark of Alzheimers disease. The research reveals the molecular mechanisms by ... In the mouse model of Alzheimers disease, copper accumulated in brain capillaries and, unlike in control mice, in the ...
Compounds fend off Alzheimer's disease amyloid pathology | EurekAlert! Science News
Compounds fend off Alzheimers disease amyloid pathology. University of California - San Diego ... Alzheimers disease.. "They could be used like statins are used today to prevent heart disease," said Tanzi. "If there was pre- ... have been linked to the creation of beta-amyloid plaques in Alzheimers disease, a neurodegenerative condition that afflicts ... Amyloid plaques are tell-tale protein deposits found abundantly in the brains of Alzheimers patients. The plaques, along with ...
Alzheimer's Disease: Amyloid 'Proponents' Soldier On | MedPage Today
The failure of yet another anti-amyloid drug for Alzheimers disease in phase III trials this summer turned out not to be the ... Alzheimers Disease: Amyloid Proponents Soldier On. - The failure of yet another anti-amyloid drug for Alzheimers disease in ... Even staunch advocates of the so-called amyloid hypothesis in Alzheimers disease -- which holds that beta-amyloid protein ... In an interview with MedPage Today, he said that beta-amyloid is undoubtedly a factor in the pathology of Alzheimers disease. ...
Alzheimer's disease: How amyloid aggregates alter neuronal function | EurekAlert! Science News
While the harmful effects of amyloid peptide aggregates observed in Alzheimers disease are well established, the mechanism ... Alzheimers disease: How amyloid aggregates alter neuronal function. CNRS. Journal. Cell Reports. Keywords. *ALZHEIMERS ... Alzheimers disease, which affects nearly a million French people, is characterized by a premature alteration of the patients ... mechanism that links amyloid aggregates and deficient synaptic function observed in animal models of Alzheimers disease: ...
The amyloid hypothesis of Alzheimer's disease at 25 years. - PubMed - NCBI
The amyloid hypothesis of Alzheimers disease at 25 years.. Selkoe DJ1, Hardy J2. ... often initiating factor in Alzheimers disease (AD). Confirmation that presenilin is the catalytic site of γ-secretase has ... Aβ, amyloid β‐protein; FDG, fluorodeoxyglucose; MCI, mild cognitive impairment. (Adapted from Fig 6 of Jack et al, .) ... Despite continuing debate about the amyloid β-protein (or Aβ hypothesis, new lines of evidence from laboratories and clinics ...
Analysis of Neurotoxic Beta Amyloid Peptides in Alzheimer's Disease
This article briefly explains the production of Aß from amyloid precursor protein (APP). ... Alzheimers disease is characterized by the presence of neurotoxic beta amyloid (Aß) deposits in the brain. ... Alzheimers disease is characterized by the presence of neurotoxic beta amyloid (Aß) deposits in the brain. This article ... Analysis of Neurotoxic Beta Amyloid Peptides in Alzheimers Disease. *Download PDF Copy ...
Amyloid-beta-directed immunotherapy for Alzheimer's disease
Amyloid-beta-directed immunotherapy for Alzheimers disease. Lannfelt, Lars Uppsala University, Disciplinary Domain of Medicine ... Alzheimers disease, amyloid-beta, clinical trials, immunotherapy National Category Geriatrics Medical and Health Sciences ... Current treatment options for Alzheimers disease (AD) are limited to medications that reduce dementia symptoms. Given the ... anti-amyloid immunotherapy remains one of the most promising emerging strategies for developing disease-modifying treatments ...
Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4)
... can slow memory and cognitive decline in older individuals who do not yet show symptoms of Alzheimers disease cognitive ... To test whether an anti-amyloid investigational drug, solanezumab, ... a protein that forms plaques in the brains of people with Alzheimer disease. Participants who have normal thinking and memory ... which places them at risk for memory loss and cognitive decline associated with Alzheimers disease. The study will test the ...
Free Heme and Amyloid-β: A Fatal Liaison in Alzheimer's Disease. - PubMed - NCBI
Alzheimers disease; Aβ-heme complexes; amyloid-β fibrillation; amyloid-β toxicity; free heme; hemolysis; peroxidase activity ... Free Heme and Amyloid-β: A Fatal Liaison in Alzheimers Disease.. Chiziane E1, Telemann H1, Krueger M2, Adler J1, Arnhold J1, ... While the etiology of Alzheimers disease (AD) is still unknown, an increased formation of amyloid-β (Aβ) peptide and oxidative ... As illustrated by selected in vivo measurements on a mouse model of AD, the disease is also characterized by Aβ-derived ...
Alzheimer Disease Neurons With Amyloid Plaques Stock Photo & More Pictures of 2015 | iStock
Refining Models of Amyloid Accumulation in Alzheimer's Disease | ALZFORUM
Refining Models of Amyloid Accumulation in Alzheimers Disease Go to another part. Series - Alzheimers Association ... Independent information from cerebrospinal fluid amyloid-β and florbetapir imaging in Alzheimers disease. Brain. 2015 Mar;138( ... Striatal amyloid plaque density predicts braak neurofibrillary stage and clinicopathological Alzheimers disease: implications ... In these cohorts, amyloid PET scans detected striatal amyloid only when cortical amyloid was high, in agreement with postmortem ...
Amyloid precursor protein and Alzheimer's disease :: DNA Learning Center
Alzheimers disease. An overview of Alzheimers disease-related content on Genes to Cognition Online.. SOURCE: G2C. ... What is Alzheimers disease?. Professor Kenneth Kosik defines Alzheimers disease as a slowly progressing illness that ... in a few rare cases of the disease, mutations in the amyloid precursor gene can lead to early-onset Alzheimers disease. For ... Beta-amyloid Plaques. Alzheimers disease is characterized by abnormal plaques and tangles in the brains of patients.. SOURCE: ...
Amyloid PET method works well for detecting early signs of Alzheimer's disease
A method for detecting early signs of Alzheimers disease using amyloid PET imaging works as well as the previously used ... Amyloid PET method works well for detecting early signs of Alzheimers disease. *Download PDF Copy ... A method for detecting early signs of Alzheimers disease using amyloid PET imaging works as well as the previously used ... Tags: Alzheimers Disease, Brain, Drugs, G-Protein, Healthcare, Imaging, Neurology, Protein, Research, Tomography ...
Amyloid formation may link Alzheimer disease and type 2 diabetes
ALZHEIMER »Alzheimer disease »Amyloid »Elsevier »T2D »fibril »fibrils »pancreas »proteins »type 2 diabetes ... Further reports about: , ALZHEIMER , Alzheimer disease , Amyloid , Elsevier , T2D , fibril , fibrils , pancreas , proteins , ... Amyloid formation may link Alzheimer disease and type 2 diabetes. 17.02.2015 ... Islet amyloid can be found in islets of Langerhans in almost all patients with T2D. Islet amyloid is made up of islet amyloid ...
Decreased Clearance of CNS β-Amyloid in Alzheimer's Disease | Science
The amyloid hypothesis of Alzheimers disease: Progress and problems on the road to therapeutics. Science 297, 353 (2002). doi: ... Alzheimers disease is hypothesized to be caused by an imbalance between β-amyloid (Aβ) production and clearance that leads to ... Cerebral amyloid angiopathy in the brains of patients with Alzheimers disease: the CERAD experience, Part XV. Neurology 46, ... Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimers disease is increased in vivo by the ...
β Amyloid Degradation: The Forgotten Half of Alzheimer's Disease | ALZFORUM
β Amyloid Degradation: The Forgotten Half of Alzheimers Disease. Thursday, September 12, 2002 at 12:00 AM US EDT. ... Degradation of the Alzheimers amyloid β peptide by endothelin-converting enzyme. J Biol Chem. 2001 Jul 6;276(27):24540-8. ... Yet, looking back on the history of Alzheimers disease research, there has been almost exclusive focus on the mechanisms of β- ... Kurochkin IV, Goto S. Alzheimers β-amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme. ...
Amyloid-β and hyperphosphorylated tau synergy drives metabolic decline in preclinical Alzheimer's disease
This study was designed to test the interaction between amyloid-β and tau proteins as a determinant of metabolic decline in ... preclinical Alzheimers disease (AD). We assessed 120 cognitively normal individuals with [,sup,18,/sup,F]florbetapir positron ... Amyloid-β and hyperphosphorylated tau synergy drives metabolic decline in preclinical Alzheimers disease Mol Psychiatry. 2017 ... 7 Alzheimers Disease Research Unit, The McGill University Research Centre for Studies in Aging, Montreal, McGill University, ...
The role of pro-inflammatory S100A9 in Alzheimer's disease amyloid-neuroinflammatory cascade | SpringerLink
The amyloid cascade with the leading role of amyloid-β (Aβ) peptides remains a central concept of Alzheimers disease (AD) ... Selkoe DJ (2000) Toward a comprehensive theory for Alzheimers disease. Hypothesis: Alzheimers disease is caused by the ... Aβ Alzheimers disease Amyloid Cytotoxicity Neuroinflammation S100A9 Traumatic brain injury C. Wang, A.G. Klechikov and A.L. ... Schlachetzki JC, Hull M (2009) Microglial activation in Alzheimers disease. Curr Alzheimer Res 6(6):554-563PubMedCrossRef ...
Alzheimer's Disease Therapeutics: Alternatives to Amyloid 2019 | The New York Academy of Sciences
... emerging disease mechanisms, and strategies to develop novel therapeutic approaches. ... This conference will consider the landscape of Alzheimers disease research including the current state of the amyloid ... For the last 25 years, research in Alzheimers disease has focused on amyloid as the key driver of disease pathogenesis. ... Alzheimers Disease Therapeutics: Alternatives to Amyloid 2019. Wednesday, November 20, 2019, 8:30 AM - 6:05 PM EST. The New ...
Bexarotene Amyloid Treatment for Alzheimer's Disease - Full Text View - ClinicalTrials.gov
Alzheimer Disease. Dementia. Brain Diseases. Central Nervous System Diseases. Nervous System Diseases. Tauopathies. ... Bexarotene Amyloid Treatment for Alzheimers Disease (BEAT-AD). The safety and scientific validity of this study is the ... The study drug bexarotene is an FDA approved anti-cancer agent but is not approved for use in Alzheimers disease. Bexarotene ... Change in the Ratio of Beta Amyloid 42 to Beta Amyloid 40 in All Subjects [ Time Frame: Baseline to Week 4 ]. This measures the ...
Amyloid, the Presenilins and Alzheimer's Disease
... autosomal Alzheimers disease. A series of mis-sense mutations (with one exception) in each of these genes has been shown to ... cause disease in a fully penetrant fashion. It has recently been shown, both i … ... Various mutations in the amyloid protein precursor and presenilin genes can lead to early onset, ... Amyloid, the Presenilins and Alzheimers Disease Trends Neurosci. 1997 Apr;20(4):154-9. doi: 10.1016/s0166-2236(96)01030-2. ...
Alzheimer's Disease Researchers Find Clues to Toxic Forms of Amyloid Beta
With a better understanding of the molecular mechanisms underlying the Alzheimers disease, researchers hope to identify new ... Alzheimers Disease. Alzheimers disease is a progressive neurodegenerative disease affecting memory and thinking and making ... Alzheimers Disease Researchers Find Clues to Toxic Forms of Amyloid Beta. by Dr. Trupti Shirole on June 11, 2016 at 5:46 PM ... Genetics of Alzheimer s disease. There are numerous genes that have been discovered that are associated with Alzheimer s ...
Amyloid β oligomers in Alzheimer's disease pathogenesis, treatment, and diagnosis | SpringerLink
Parkinsons and Alzheimers. Over the past 15 years, there has been a paradigm shift in understanding the structural ... Protein aggregation is common to dozens of diseases including prionoses, diabetes, ... Lipid rafts mediate amyloid-induced calcium dyshomeostasis and oxidative stress in Alzheimers disease. Curr Alzheimer Res 10(2 ... Amyloid-beta and tau pathology of Alzheimers disease induced by diabetes in a rabbit animal model. J Alzheimers Dis 32(2):291 ...
JCI - The role of cerebral amyloid β accumulation in common forms of Alzheimer disease
The role of cerebral amyloid β accumulation in common forms of Alzheimer disease. ... The role of cerebral amyloid β accumulation in common forms of Alzheimer disease. ... For approximately 80 years following Alzheimers description of the disease that bears his name, a gulf divided researchers who ... the aggregates that accumulate in the interstices of the brains of patients with autosomal dominant familial Alzheimer disease ...
RCSB PDB - 1IYT: Solution structure of the Alzheimer's disease amyloid beta-peptide (1-42)
The major components of neuritic plaques found in Alzheimer disease (AD) are peptides known as amyloid beta-peptides (Abeta), ... The major components of neuritic plaques found in Alzheimer disease (AD) are peptides known as amyloid beta-peptides (Abeta), ... Solution structure of the Alzheimers disease amyloid beta-peptide (1-42). *DOI: 10.2210/pdb1IYT/pdb ... Solution structure of the Alzheimer amyloid beta-peptide (1-42) in an apolar microenvironment. Similarity with a virus fusion ...
Alzheimer's Disease Amyloid Plaque (TWBW734AF) by 3DBiology
Alzheimers Disease Amyloid Plaque (TWBW734AF) by 3DBiology on Shapeways. Learn more before you buy, or discover other cool ... Alzheimers Disease Amyloid Plaque Biology Cell Disease Molecular Biology Molecular Models Protein ... Amyloid beta (Aβ or Abeta) denotes peptides of 36-43 amino acids that are crucially involved in Alzheimers disease as the main ... The other protein implicated in Alzheimers disease, tau protein, also forms such prion-like misfolded oligomers, and there is ...
Novel culture system replicates course of Alzheimer's disease, confirms amyloid hypothesis | FierceBiotech
... of Alzheimers disease that express the gene variants causing the inherited early-onset form of the disease do develop amyloid ... the amyloid precursor protein and presenilin 1 - known to underlie early-onset familial Alzheimers Disease (FAD). Both of ... In this new system that we call Alzheimers-in-a-dish, weve been able to show for the first time that amyloid deposition is ... Cultured neurons from human patients with Alzheimers exhibit elevated levels of the toxic form of amyloid found in plaques and ...
Amyloid Plaques Containing Nucleic Acids Drive Neuroinflammation in Alzheimer's Disease
Amyloid-β aggregates are present in the early stages of the condition, while... ... Alzheimers disease is characterized by the presence of protein aggregates in the brain. These are misfolded and altered ... Gaussian Discriminative Component Analysis for Early Detection of Alzheimers Disease: A Supervised Dimensionality Reduction ... Alzheimers disease is characterized by the presence of protein aggregates in the brain. These are misfolded and altered ...
Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimer's Disease
Alzheimers disease is a neurodegenerative condition characterized by an accumulation of toxic amyloid beta- (A. 𝛽. -)peptides ... Zinc Metalloproteinases and Amyloid Beta-Peptide Metabolism: The Positive Side of Proteolysis in Alzheimers Disease. Mallory ... It is the role of zinc metalloproteinases in this "positive side of proteolysis in Alzheimers disease" that is discussed in ... peptides are produced by aspartyl proteinase-mediated cleavage of the larger amyloid precursor protein (APP). In contrast to ...
PrecursorNeurofibrillaryOligomersNeurodegenerativePlaqueInsolubleBrainsNeurodegenerationKnown as amyloidExtracellularAggregatesCascade hypothesisNeuronalCognitive impairmentSenile plaquesSolubleIslet amyloid polVivoBuild-up of amyloid plaquesDeposition of beta-amyloid plaquesCerebral amyloidBiomarkerFormation of amyloid plaquesIntracellularToxicityAbnormalBuildup of amyloid plaquesStabilising the formation of amyloidTherapeuticAntibodiesFibril formationResearchersAngiopathyPositron emission tBurdenPathogenicTherapeutics
- Islet amyloid is made up of islet amyloid polypeptide (IAPP), which is derived from its precursor proIAPP. (innovations-report.com)
- Since 1990, the discoveries of missense mutations in the Aβ peptide precursor (APP) and the APP-cleaving enzyme presenilin 1 (PS1) have enabled much progress in understanding the molecular, cellular, and tissue pathology of the aggregates that accumulate in the interstices of the brains of patients with autosomal dominant familial Alzheimer disease (AD). (jci.org)
- The major components of neuritic plaques found in Alzheimer disease (AD) are peptides known as amyloid beta-peptides (Abeta), which derive from the proteolitic cleavage of the amyloid precursor proteins. (rcsb.org)
- Tg2576 mice (Tg(APPSWE)2576Kha), which express human [beta]-amyloid precursor proteins (hAPP) containing the K670N and M671L mutations on a 129S6 genetic background, were purchased from Taconic Farms, Inc. (Hudson, NY, USA) . (thefreelibrary.com)
- Clinically, attempts to understand AD have focused on trying to predict the presence of, and more recently demonstrate the presence of, its characteristic amyloid plaque and neurofibrillary tangle pathologies. (springer.com)
- In fact, the regions displaying the metabolic decline reported here were confined to brain networks affected early by amyloid-β plaques and neurofibrillary tangles. (nih.gov)
- AD is pathologically defined by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) within the brain. (jneurosci.org)
- The preclinical stage of AD is characterized by β-amyloid (Aβ) aggregation into amyloid plaques and tau phosphorylation and aggregation into neurofibrillary tangles. (frontiersin.org)
- AD is characterized histopathologically by the presence and abundance of two different abnormal aggregated proteins, amyloid plaques and neurofibrillary tangles, in brain tissue ( Fig 1 ) [ 3 ]. (pubmedcentralcanada.ca)
- To test the hypothesis that the association of amyloid load with clinical Alzheimer disease (AD) and cognitive impairment is mediated through neurofibrillary tangles. (unboundmedicine.com)
- The percent area occupied by amyloid-beta and the density of neurofibrillary tangles were quantified from 6 brain regions and averaged to yield summary measures of amyloid load and neurofibrillary tangles. (unboundmedicine.com)
- Multivariate regression analyses were used to simultaneously examine the effects of amyloid load and neurofibrillary tangles on clinically diagnosed AD and level of cognition. (unboundmedicine.com)
- These findings are consistent with a sequence of pathologic events whereby the effect of amyloid deposition on clinical disease is mediated by neurofibrillary tangles. (unboundmedicine.com)
- From a histological viewpoint, the progression of AD is associated with 3 cardinal neuropathological features: the accumulation of extracellular senile plaques which is mediated by amyloid-beta (Aβ), intracellular neurofibrillary tangles (NFT) and synaptic degeneration (fig. 1 ) [ 13 , 14 ]. (karger.com)
- The distinctive histopathologic hallmarks of Alzheimer disease (AD) are the neuritic plaques and the neurofibrillary tangles (NFT). (ajnr.org)
- Design Using a recently developed AD-like pathology with amyloid and neurofibrillary tangles (ADLP APT ) transgenic mouse model of AD, which shows amyloid plaques, neurofibrillary tangles and reactive gliosis in their brains along with memory deficits, we examined the impact of the gut microbiota on AD pathogenesis. (bmj.com)
- Both frequent transfer and transplantation of the faecal microbiota from WT mice into ADLP APT mice ameliorated the formation of amyloid β plaques and neurofibrillary tangles, glial reactivity and cognitive impairment. (bmj.com)
- The amyloid hypothesis proposes that AD is caused by an imbalance between Aβ production and clearance ( 1 ), resulting in increased amounts of Aβ in various forms such as monomers, oligomers, insoluble fibrils, and plaques in the central nervous system (CNS). (sciencemag.org)
- This subtle change stabilizes a prefibrillary intermediate that has higher toxicity," he said, noting that the stable intermediate could be a very useful tool for investigating the neurotoxic effects of amyloid beta oligomers. (medindia.net)
- When over-secreted, some proteins have a higher propensity to stick to one another, forming small aggregates, called oligomers, fibrils and amyloids. (ucdavis.edu)
- however, there are also soluble forms of amyloid beta, or oligomers, that may decisively contribute to neural degeneration. (rxpgnews.com)
- We now understand much more about the underlying pathogenesis of the disease, as well as the role of toxic amyloid oligomers in the cascade of Alzheimer's, and the patient populations most likely to respond to amyloid-targeted therapies. (businesswire.com)
- The oral presentation reviews the central role of toxic beta amyloid (Aβ) oligomers in the development and progression of AD, highlighting Alzheon's discovery of the novel mechanism of action of tramiprosate, the active agent in optimized prodrug ALZ-801 that blocks formation of Aβ oligomers. (businesswire.com)
- Based on the recent series of new scientific and clinical data from Alzheon, we have established ALZ-801 as a pioneering small molecule anti-amyloid therapy, which directly inhibits the formation of toxic oligomers that are the pathogenic driver of the development and progression of Alzheimer's," said Martin Tolar, MD, PhD, Founder, President and CEO of Alzheon. (businesswire.com)
- Alzheimer''s disease is a progressive neurodegenerative disease affecting memory and thinking and making the person increasingly dependent on others. (medindia.net)
- Using the system they developed, investigators from the Genetics and Aging Research Unit at Massachusetts General Hospital (MGH) now provide the first clear evidence supporting the hypothesis that deposition of beta-amyloid plaques in the brain is the first step in a cascade leading to the devastating neurodegenerative disease. (fiercebiotech.com)
- This new system - which can be adapted to other neurodegenerative disorders - should revolutionize drug discovery in terms of speed, costs and physiologic relevance to disease,' says Tanzi. (fiercebiotech.com)
- Alzheimer s disease is a progressive neurodegenerative disorder, affecting 4.5 million to 5 million adults in the United States. (rxpgnews.com)
- Frequently encountered in the elderly, Alzheimer's is considered a neurodegenerative disease, which means that it is accompanied by a significant, progressive loss of neurons and their nerve endings, or synapses. (medicalxpress.com)
- This was an intriguing finding because IL1RAP is known to play a central role in the activity of microglia, the immune system cells that act as the brain's "garbage disposal system" and the focus of heavy investigation in a variety of neurodegenerative diseases," said Vijay K. Ramanan, M.D., Ph.D., postdoctoral researcher at the IU School of Medicine. (healthcanal.com)
- Its wide healing properties make it increasingly interesting to scientists, with potential uses in the treatment of cancers, arthritis, various cardiovascular diseases, and neurodegenerative diseases. (scirp.org)
- Their study showed that these cells, called microglia, contribute to the neuronal and memory deficits seen in this neurodegenerative disease. (fightaging.org)
- Although the compound swept away microglia, the beta-amyloid remained, raising new questions about the part these plaques play in Alzheimer's neurodegenerative process. (fightaging.org)
- Background and Purpose- White-matter hyperintensities (WMHs) detected by magnetic resonance imaging are thought to represent the effects of cerebral small-vessel disease and neurodegenerative changes. (ahajournals.org)
- This work was supported by funding from the EPSRC and Wellcome Trust-MRC Neurodegenerative Disease Initiative Grant. (springer.com)
- Such amyloids have been associated with more than 50 human diseases, known as amyloidosis, and may play a role in some neurodegenerative disorders. (wikipedia.org)
- Talks pinned down the rate of amyloid accumulation, highlighted a region where plaque formation might correlate with imminent cognitive decline, and clarified the temporal relationship between Aβ signals in the CSF and in the brain. (alzforum.org)
- Recent experimental evidence indicates that in the cortex, in addition to the silencing of a fraction of neurons, other neurons are hyperactive in amyloid-β (Aβ) plaque-enriched regions. (pnas.org)
- We proposed quantitative Aβ-weighted cortical thickness analysis to investigate the regional relationship between cortical thinning and amyloid plaque deposition using magnetic resonance (MR) and Pittsburg Compound B (PiB) positron emission tomography (PET) images in patients with AD, mild cognitive impairment (MCI), and subjects with normal cognition. (sigmaaldrich.com)
- The ability to quantify regional Aβ plaque load in the brains of living human subjects has provided a means to begin to apply this technology as a diagnostic agent to detect regional concentrations of Aβ plaques and as a surrogate marker of therapeutic efficacy in anti-amyloid drug trials. (pubmedcentralcanada.ca)
- Several teams of scientists around the world are working on finding ways to prevent amyloid plaque formation in the human brain. (medicalxpress.com)
- They could be a good alternative to the currently pursued antibody-based approaches as therapeutics against Alzheimer's amyloid plaque formation because they are easy to produce, have promising properties and, due to their peptidic nature, they will be significantly cheaper than antibodies," says Professor Kapurniotu. (medicalxpress.com)
- A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. (diva-portal.org)
- This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. (diva-portal.org)
- Biochemical analysis revealed that the Ube3a-deficient AD mice had significantly reduced level of Aβ generation and amyloid plaque formation in their brain compared with age-matched AD mice and this effect could be due to the increased activity of α-secretase, ADAM10 (a disintegrin and metalloproteinase-10) that shift the proteolysis of APP towards non-amyloidogenic pathway. (ovid.com)
- After 20 years of failed amyloid plaque research it's time for the medical community to stop wasting its time and change direction. (naturalnews.com)
- An elevated CSF tau level is considered an in vivo marker of NFT, and a low CSF amyloid-β 1-42 (Aβ 1-42 ) level as a marker of Aβ plaque deposition in the brain of patients with AD. (ajnr.org)
- Amyloid plaque itself has been reported to induce no magnetic susceptibility effect. (berkeley.edu)
- Individual beta amyloid plaque can also be visualized ex vivo in high resolution susceptibility maps. (berkeley.edu)
- The amyloid plaque intensity was reduced in a concentration dependent manner by CTB-MBP incubation with human AD and 3xTgAD mice brain sections. (arvojournals.org)
- Preliminary results indicate that mice, which have received the AAV-shRNA targeting PICALM, present an increase in amyloid plaque load in the cortex compared to non-injected animals, suggesting that PICALM is indeed involved in the regulation of the amyloid metabolism in vivo. (epfl.ch)
- In people whose brains were at the threshold for amyloid positivity (an SUVR of 1.45 in this case) when they died, the researchers measured about 3.2 μg Aβ per gram of frontal cortex. (alzforum.org)
- Atul Deshpande, a graduate student in Busciglio s laboratory, tested one preparation of fibrillar amyloid beta and two soluble ones, which resemble the types found in the brains of Alzheimer s patients. (rxpgnews.com)
- An international team of researchers has found different disease type associations with distinct amyloid-beta prion strains in the brains of dead Alzheimer's patients. (medicalxpress.com)
- Amyloid is deposited in the walls of arteries and capillaries as cerebral amyloid angiopathy (CAA) in the brains of older individuals and of those with Alzheimer disease (AD). (soton.ac.uk)
- The brains of millions of people suffering from Alzheimer´s disease are slowly and inescapably being depleted of neurons. (irbbarcelona.org)
- 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)
- The interaction found in this study further support the framework that amyloid-β and hyperphosphorylated tau aggregates synergistically interact to cause downstream AD neurodegeneration. (nih.gov)
- While we were successful in removing the elevated microglia resulting from beta-amyloid, further research is required to better understand the link among beta-amyloid, inflammation and neurodegeneration in Alzheimer's. (fightaging.org)
Known as amyloid2
- The goal for researchers now is to continue studying amyloid aggregates, especially by trying to prevent their interaction with CamKII and the loss of synapses observed during the disease. (eurekalert.org)
- Cross-seeding by other amyloid aggregates or perhaps by other types of aggregates offers one possible mechanism for initiation of amyloid formation. (innovations-report.com)
- Amyloid-β aggregates are present in the early stages of the condition, while tau aggregates cause much greater harm and cell death in the later stages. (medworm.com)
- The description of the barrel-shaped aggregates in the journal Proceedings of the National Academy of Sciences (PNAS) is the first step to establish the involvement of this aggregate in Alzheimer´s disease. (irbbarcelona.org)
- It is argued that these genetic and molecular biological data provide strong support for the veracity of the 'amyloid cascade hypothesis' for disease pathogenesis, and that this hypothesis offers a coherent framework for drug discovery. (nih.gov)
- While several lines of evidence that support the amyloid cascade hypothesis, there are also a number of challenges to it. (verywellhealth.com)
- The experiments conducted at UCI showed that the soluble forms of amyloid beta are much more toxic and lead to neuronal death in as little as 12 hours. (rxpgnews.com)
- One theory is it binds to neuronal connections, or gateways into the cell, and gives soluble amyloid beta easier, quicker access into the neuron. (rxpgnews.com)
- When drug giant Eli Lilly announced in August that both EXPEDITION trials of its anti-amyloid drug solanezumab had failed to show a significant benefit, many in the field thought that would be the end of the line for such agents, at least for patients showing clear signs of cognitive impairment. (medpagetoday.com)
- According to the scientists, previous research has shown that the brain levels of soluble amyloid beta appear to correlate better with severity of cognitive impairment than the number and density of plaques found in the brain. (rxpgnews.com)
- These results suggest that impaired nitric oxide bioavailability exacerbates the pathophysiology of Alzheimer disease, essentially impacting amyloid load and cognitive impairment, independently of l -NAME-induced hypertension. (ahajournals.org)
- Methods- We examined the pattern of WMHs by T2/fluid-attenuated inversion recovery-weighted magnetic resonance imaging in 3 groups of subjects: cerebral amyloid angiopathy (n=32), Alzheimer disease or mild cognitive impairment (n=41), and healthy aging (n=29). (ahajournals.org)
- Results- Although WMH volume was greater in cerebral amyloid angiopathy and Alzheimer disease/mild cognitive impairment than in healthy aging, there was no consistent difference in the spatial distributions when controlling for total WMH volume. (ahajournals.org)
- 2,4 Greater WMH burdens have been found in neurologic syndromes such as vascular dementia, cerebral amyloid angiopathy (CAA), and Alzheimer disease (AD) and mild cognitive impairment (MCI). (ahajournals.org)
- Not known is whether the soluble amyloid beta in the Alzheimer brain eventually turns into the fibrillar kind, or whether the two are completely different. (rxpgnews.com)
- For example, it might be dangerous to create compounds that target fibrillar amyloid and try to break them up, because if the fibers dissolve into the soluble form, that could actually speed up cell death and the onset of dementia rather than treat it. (rxpgnews.com)
- Then, the more soluble beta amyloid is present, the more severe and rapid the onset of the disease. (rxpgnews.com)
- Researchers now will have to determine why the soluble form of beta amyloid is so much more toxic. (rxpgnews.com)
Islet amyloid pol1
- Likewise, compounds aimed at inhibiting secretase enzymes responsible for producing beta-amyloid in vivo were disappointing. (medpagetoday.com)
- As illustrated by selected in vivo measurements on a mouse model of AD, the disease is also characterized by Aβ-derived microvessel destructions and hemolytic processes. (nih.gov)
- It has recently been shown, both in vivo and in model systems, that tissues expressing these mutations have increased production of amyloid (A beta) ending at residue 42. (nih.gov)
- Researchers from Keele University have shown that physiologically-significant concentrations of SAP promote the deposition of amyloid beta under conditions approaching those found in vivo. (medicalxpress.com)
- Over a period of 18 months, we showed that QSM can be used to longitudinally monitor beta amyloid accumulation and accompanied iron deposition in vivo. (berkeley.edu)
Build-up of amyloid plaques2
- The drug, designed to reduce the build-up of amyloid plaques on the brain, was studied in 2,129 patients diagnosed with mild dementia due to Alzheimer's participated in the multi-national EXPEDITION3 trial . (verywellhealth.com)
- Though it is true that many Alzheimer's patients' autopsies do reveal a build-up of amyloid plaques on the brain, this is by no means a totally consistent trend. (naturalnews.com)
Deposition of beta-amyloid plaques1
- Cerebral amyloid angiopathy (CAA) is a distinctive abnormality of small cerebral blood vessels, one that has intrigued neuroscientists for decades. (barnesandnoble.com)
- The Cerebral Amyloid Angiopathy (CAA) Resource This website is intended as a resource for both patients and families suffering from CAA and the investigators and clinicians who work in this field. (alzheimer-europe.org)
- Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. (semanticscholar.org)
- Cerebral amyloid angiopathies: a pathologic, biochemical, and genetic view. (semanticscholar.org)
- Capillary cerebral amyloid angiopathy is associated with vessel occlusion and cerebral blood flow disturbances. (semanticscholar.org)
- However, there are other types: the "Icelandic type" is associated with Cystatin C the "British type" is associated with ITM2B Research is currently being conducted to determine if there is a link between cerebral amyloid angiopathy and ingestion of excessive quantities of aluminum. (wikipedia.org)
- The aim in cerebral amyloid angiopathy is to treat the symptoms, as there is no current cure. (wikipedia.org)
Formation of amyloid plaques1
- Instead, they are defined as "close relatives" of amyloid because of their predominantly intracellular or intraneuronal locations. (pubmedcentralcanada.ca)
- Recently this definition has come into question as some classic, amyloid species have been observed in distinctly intracellular locations. (wikipedia.org)
- The new findings underscore the importance of the amino acid at position 22 for amyloid beta toxicity. (medindia.net)
- RxPG] Researchers at UC Irvine have shown that different forms of amyloid beta lead to neural damage in different ways, leading to an increasingly complex view of amyloid toxicity in the Alzheimer brain. (rxpgnews.com)
Buildup of amyloid plaques2
- 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)
- In essence, reduced amyloid burden in cerebral blood vessels, or CAA, was able to preserve cognitive function despite the buildup of amyloid plaques in the brain tissue," says Dr. Iadecola, who is also a neurologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. (healthcanal.com)
Stabilising the formation of amyloid1
- The finding could modify the way therapeutic approaches for the treatment of Alzheimer s disease are designed. (rxpgnews.com)
- This complexity of the amyloid beta species will require more sophisticated therapeutic approaches. (rxpgnews.com)
- These will be decisive experiments for the validation of this specific amyloid-beta aggregate as a therapeutic target. (irbbarcelona.org)
- On top of better performances in the water maze, the vaccinated mice were tested to have a higher level of Amyloid-β antibodies. (globenewswire.com)
- The researchers attached antibodies that specifically detect amyloid beta onto a tiny electrode, zapped it with a small amount of voltage and measured the resulting current. (wustl.edu)
- The improved results that we have now obtained with anti-amyloid antibodies are largely due to the fact that higher doses of these treatments are being used," explains Alzheimer's expert Elizabeth Stögmann. (selectscience.net)
- Researchers also provided more evidence that inflammatory processes cause the brain to swell early in AD, which could complicate the interpretation of brain volume changes during disease progression and treatment. (alzforum.org)
- Researchers first injected transgenic mice expressing human IAPP with preformed fibrils of synthetic IAPP, proIAPP, or beta-amyloid. (innovations-report.com)
- With a better understanding of the molecular mechanisms underlying the disease, researchers hope to identify new targets for drug development efforts. (medindia.net)
- Currently, Amyloid-β buildup in the brain is believed to be the cause of Alzheimer's among many researchers. (globenewswire.com)
- Amyloid beta accumulation is one of two hallmarks of Alzheimer s disease and is considered a major target for researchers looking into therapies for the treatment of the disease. (rxpgnews.com)
- Researchers are increasingly focused on mechanisms involved with the deposit and clearance of amyloid plaques, particularly in early stages when symptoms are mild or not yet present. (healthcanal.com)
- And he notes that Harvard researchers have theorized that amyloid plaques are part of an immune response, and may even be beneficial. (naturalnews.com)
- Since mouse amyloid beta, unlike the human version, does not produce a current when exposed to voltage, the researchers used mice genetically modified to produce human amyloid beta. (wustl.edu)
- Researchers found that flushing away the abundant inflammatory cells produced in reaction to beta-amyloid plaques restored memory function in test mice. (fightaging.org)