Amyloid
Amyloid beta-Peptides
Serum Amyloid A Protein
Amyloid beta-Protein Precursor
Islet Amyloid Polypeptide
Amyloidosis
Cerebral Amyloid Angiopathy
Serum Amyloid P-Component
Amyloid Neuropathies
Amyloid Precursor Protein Secretases
Alzheimer Disease
Congo Red
Amyloid Neuropathies, Familial
Prealbumin
Peptide Fragments
Aspartic Acid Endopeptidases
Presenilin-1
Mice, Transgenic
Brain
Cerebral Amyloid Angiopathy, Familial
Prions
Protein Structure, Secondary
Neurofibrillary Tangles
Amino Acid Sequence
tau Proteins
Molecular Sequence Data
Protein Multimerization
Microscopy, Electron, Transmission
Microscopy, Atomic Force
Protease Nexins
beta 2-Microglobulin
Neurons
Disease Models, Animal
Endopeptidases
Circular Dichroism
Insulysin
Microscopy, Electron
Protein Conformation
Presenilin-2
Protein Binding
Mutation
Models, Molecular
Protein Structure, Tertiary
Protein Structure, Quaternary
Peptides
Hippocampus
alpha-Synuclein
Cerebral Cortex
Spectroscopy, Fourier Transform Infrared
Immunohistochemistry
Neurofibrils
Apolipoproteins E
Gerstmann-Straussler-Scheinker Disease
Peptide Termination Factors
Apolipoprotein E4
Microglia
Aging
Cells, Cultured
Presenilins
Neurodegenerative Diseases
Receptors, Islet Amyloid Polypeptide
Neprilysin
Islets of Langerhans
Protein Processing, Post-Translational
Protein Denaturation
Positron-Emission Tomography
Acute-Phase Reaction
PC12 Cells
Nuclear Magnetic Resonance, Biomolecular
Maze Learning
Enzyme-Linked Immunosorbent Assay
Solubility
Trifluoroethanol
Prion Diseases
Protein Stability
Coloring Agents
Gliosis
Membrane Proteins
Brain Chemistry
Islet amyloid polypeptide/amylin messenger RNA and protein expression in human insulinomas in relation to amyloid formation. (1/3010)
OBJECTIVE: Islet amyloid polypeptide (IAPP), also named amylin, is the predominant protein component of amyloid deposits in human islet beta cell tumours of the pancreas (insulinomas). IAPP is co-produced with insulin by islet beta cells. We investigated IAPP expression in relation to insulin expression and to amyloid formation in eleven insulinomas. DESIGN AND METHODS: RNA and protein extracts were prepared from the same pieces of tumour tissue, and from specimens of two normal human pancreata. IAPP and insulin mRNA and peptide content were quantified using Northern blot analysis and radioimmunoassay (RIA) respectively. Molecular forms of IAPP immunoreactivity were analysed by reversed-phase high-performance liquid chromatography (HPLC). The presence of islet hormones and of amyloid was assessed by (immuno)histochemical staining of paraffin sections. Plasma levels of IAPP and insulin prior to tumour resection were determined by RIA. RESULTS: IAPP and insulin mRNA and peptide content varied widely between the tumour specimens, and there was considerable intratumour heterogeneity of peptide content. HPLC analysis indicated correct proteolytic processing of the IAPP precursor protein. Amyloid deposits were detected only in the three tumours with the highest IAPP content. In contrast to insulin, plasma levels of IAPP were not elevated in the insulinoma patients. CONCLUSIONS: The spectrum of hormone production by insulinomas cannot be inferred from only a few tissue sections due to intratumour heterogeneity. Expression of the IAPP and insulin genes is not coupled in insulinomas, which produce properly processed mature IAPP. In addition to IAPP overproduction, additional factors such as intracellular accumulation of IAPP are involved in amyloidogenesis in insulinomas. (+info)Prion domain initiation of amyloid formation in vitro from native Ure2p. (2/3010)
The [URE3] non-Mendelian genetic element of Saccharomyces cerevisiae is an infectious protein (prion) form of Ure2p, a regulator of nitrogen catabolism. Here, synthetic Ure2p1-65 were shown to polymerize to form filaments 40 to 45 angstroms in diameter with more than 60 percent beta sheet. Ure2p1-65 specifically induced full-length native Ure2p to copolymerize under conditions where native Ure2p alone did not polymerize. Like Ure2p in extracts of [URE3] strains, these 180- to 220-angstrom-diameter filaments were protease resistant. The Ure2p1-65-Ure2p cofilaments could seed polymerization of native Ure2p to form thicker, less regular filaments. All filaments stained with Congo Red to produce the green birefringence typical of amyloid. This self-propagating amyloid formation can explain the properties of [URE3]. (+info)Interaction of amylin with calcitonin gene-related peptide receptors in the microvasculature of the hamster cheek pouch in vivo. (3/3010)
1. This study used intravital microscopy to investigate the receptors stimulated by amylin which shares around 50% sequence homology with the vasodilator calcitonin gene-related peptide (CGRP) in the hamster cheek pouch microvasculature in vivo. 2. Receptor agonists dilated arterioles (diameters 20-40 microm). The -log of the concentrations (+/- s.e.mean; n = 8) causing 50% increase in arteriole diameter were: human betaCGRP (10.8 +/- 0.3), human alphaCGRP (10.8 +/- 0.4), rat alphaCGRP (10.4 +/- 0.3). Rat amylin and the CGRP2 receptor selective agonist [Cys(ACM2,7]-human alphaCGRP were 100 fold less potent (estimates were 8.5 +/- 0.4 and 8.2 +/- 0.3 respectively). 3. The GCRP1 receptor antagonist, CGRP8-37 (300 nmol kg(-1); i.v.) reversibly inhibited the increase in diameter evoked by human alphaCGRP (0.3 nM) from 178 +/- 22% to 59 +/- 12% (n = 8; P < 0.05) and by rat amylin (100 nM) from 138 +/- 23% to 68 +/- 24% (n = 6; P < 0.05). CGRP8-37 did not inhibit vasodilation evoked by substance P (10 nM; n = 4: P > 0.05). 4. The amylin receptor antagonist, amylin8-37 (300 nmol kg(-1); i.v.) did not significantly inhibit the increase in diameter evoked by human alphaCGRP (0.3 nM) which was 112 +/- 26% in the absence, and 90 +/- 29% in the presence of antagonist (n = 4; P < 0.05); nor that evoked by rat amylin (100 nM) which was 146 +/- 23% in the absence and 144 +/- 32% in the presence of antagonist (n = 4; P > 0.05). 5. The agonist profile for vasodilatation and the inhibition of this dilatation by CGRP8-37, although not the amylin8-37 indicates that amylin causes vasodilatation through interaction with CGRP1 receptors in the hamster cheek pouch. (+info)The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles. (4/3010)
NIDDM is characterized by islet amyloid deposits and decreased beta-cell mass. Islet amyloid is derived from the locally expressed protein islet amyloid polypeptide (IAPP). While it is now widely accepted that abnormal aggregation of IAPP has a role in beta-cell death in NIDDM, the mechanism remains unknown. We hypothesized that small IAPP aggregates, rather than mature large amyloid deposits, are cytotoxic. Consistent with this hypothesis, freshly dissolved human (h)-IAPP was cytotoxic when added to dispersed mouse and human islet cells, provoking the formation of abnormal vesicle-like membrane structures in association with vacuolization and cell death. Human islet cell death occurred by both apoptosis and necrosis, predominantly between 24 and 48 h after exposure to h-IAPP. In contrast, the addition to dispersed islet cells of matured h-IAPP containing large amyloid deposits of organized fibrils was seldom associated with vesicle-like structures or features of cell death, even though the cells were often encased in the larger amyloid deposits. Based on these observations, we hypothesized that h-IAPP cytotoxicity is mediated by membrane damage induced by early h-IAPP aggregates. Consistent with this hypothesis, application of freshly dissolved h-IAPP to voltage-clamped planar bilayer membranes (a cell-free in vitro system) also caused membrane instability manifested as a marked increase in conductance, increased membrane electrical noise, and accelerated membrane breakage, effects that were absent using matured h-IAPP or rat IAPP solutions. Light-scattering techniques showed that membrane toxicity corresponded to h-IAPP aggregates containing approximately 25-6,000 IAPP molecules, an intermediate-sized amyloid particle that we term intermediate-sized toxic amyloid particles (ISTAPs). We conclude that freshly dissolved h-IAPP is cytotoxic and that this cytotoxicity is mediated through an interaction of ISTAPs with cellular membranes. Once ISTAPs mature into amyloid deposits comprising >10(6) molecules, the capacity of h-IAPP to cause membrane instability and islet cell death is significantly reduced or abolished. These data may have implications for the mechanism of cell death in other diseases characterized by local amyloid formation (such as Alzheimer's disease). (+info)Specific gene expression in pancreatic beta-cells: cloning and characterization of differentially expressed genes. (5/3010)
Identification and characterization of genes expressed preferentially in pancreatic beta-cells will clarify the mechanisms involved in the specialized properties of these cells, as well as providing new markers of the development of type 1 diabetes. Despite major efforts, relatively few beta-cell-specific genes have been characterized. We applied representational difference analysis to identify genes expressed selectively in the pancreatic beta-cell line betaTC1 compared with the pancreatic alpha-cell line alphaTC1 and isolated 26 clones expressed at higher levels in the beta-cells than in the alpha-cells. DNA sequencing revealed that 14 corresponded to known genes (that is, present in GenBank). Only four of those genes had been shown previously to be expressed at higher levels in beta-cells (insulin, islet amyloid polypeptide, neuronatin, and protein kinase A regulatory subunit [RIalpha]). The known genes include transcription factors (STAT6) and mediators of signal transduction (guanylate cyclase). The remaining 12 genes are absent from the GenBank database or are present as expressed sequence tag (EST) sequences (4 clones). Some of the genes are expressed in a highly specific pattern-expression in betaTC1 and islet cells and in relatively few of the non-beta-cell types examined; others are expressed in most cell types tested. The identification of these differentially expressed genes may aid in attaining a clearer understanding of the mechanisms involved in beta-cell function and of the possible immunogens involved in development of type 1 diabetes. (+info)Colchicine inhibition of the first phase of amyloid synthesis in experimental animals. (6/3010)
Colchicine was found to inhibit the first phase of casein-induced synthesis of murine amyloid. When mice were treated with colchicine during the first 7 days of an amyloid induction regimen or when colchicine was given to the donor mice in a transfer model, the amyloidogenic stimulus of casein was blocked completely. Amyloid synthesis was however, not interrupted by the administration of colchicine during the last 7 days of the casein regimen nor by colchicine treatment of recipient mice in a transfer model. (+info)Ancestral origins and worldwide distribution of the PRNP 200K mutation causing familial Creutzfeldt-Jakob disease. (7/3010)
Creutzfeldt-Jakob disease (CJD) belongs to a group of prion diseases that may be infectious, sporadic, or hereditary. The 200K point mutation in the PRNP gene is the most frequent cause of hereditary CJD, accounting for >70% of families with CJD worldwide. Prevalence of the 200K variant of familial CJD is especially high in Slovakia, Chile, and Italy, and among populations of Libyan and Tunisian Jews. To study ancestral origins of the 200K mutation-associated chromosomes, we selected microsatellite markers flanking the PRNP gene on chromosome 20p12-pter and an intragenic single-nucleotide polymorphism at the PRNP codon 129. Haplotypes were constructed for 62 CJD families originating from 11 world populations. The results show that Libyan, Tunisian, Italian, Chilean, and Spanish families share a major haplotype, suggesting that the 200K mutation may have originated from a single mutational event, perhaps in Spain, and spread to all these populations with Sephardic migrants expelled from Spain in the Middle Ages. Slovakian families and a family of Polish origin show another unique haplotype. The haplotypes in families from Germany, Sicily, Austria, and Japan are different from the Mediterranean or eastern European haplotypes. On the basis of this study, we conclude that founder effect and independent mutational events are responsible for the current geographic distribution of hereditary CJD associated with the 200K mutation. (+info)Physicochemical consequences of amino acid variations that contribute to fibril formation by immunoglobulin light chains. (8/3010)
The most common form of systemic amyloidosis originates from antibody light chains. The large number of amino acid variations that distinguish amyloidogenic from nonamyloidogenic light chain proteins has impeded our understanding of the structural basis of light-chain fibril formation. Moreover, even among the subset of human light chains that are amyloidogenic, many primary structure differences are found. We compared the thermodynamic stabilities of two recombinant kappa4 light-chain variable domains (V(L)s) derived from amyloidogenic light chains with a V(L) from a benign light chain. The amyloidogenic V(L)s were significantly less stable than the benign V(L). Furthermore, only the amyloidogenic V(L)s formed fibrils under native conditions in an in vitro fibril formation assay. We used site-directed mutagenesis to examine the consequences of individual amino acid substitutions found in the amyloidogenic V(L)s on stability and fibril formation capability. Both stabilizing and destabilizing mutations were found; however, only destabilizing mutations induced fibril formation in vitro. We found that fibril formation by the benign V(L) could be induced by low concentrations of a denaturant. This indicates that there are no structural or sequence-specific features of the benign V(L) that are incompatible with fibril formation, other than its greater stability. These studies demonstrate that the V(L) beta-domain structure is vulnerable to destabilizing mutations at a number of sites, including complementarity determining regions (CDRs), and that loss of variable domain stability is a major driving force in fibril formation. (+info)The term "amyloid" refers specifically to the type of protein aggregate that forms these plaques, and is derived from the Greek word for "flour-like." Amyloidosis is the general term used to describe the condition of having amyloid deposits in the body, while Alzheimer's disease is a specific type of amyloidosis that is characterized by the accumulation of beta-amyloid peptides in the brain.
Plaques, amyloid play a central role in the pathogenesis of many neurodegenerative diseases, and understanding their formation and clearance is an area of ongoing research. In addition to their role in Alzheimer's disease, amyloid plaques have been implicated in other conditions such as cerebral amyloid angiopathy, primary lateral sclerosis, and progressive supranuclear palsy.
Plaques, amyloid are composed of a variety of proteins, including beta-amyloid peptides, tau protein, and apolipoprotein E (apoE). The composition and structure of these plaques can vary depending on the underlying disease, and their presence is often associated with inflammation and oxidative stress.
In addition to their role in neurodegeneration, amyloid plaques have been implicated in other diseases such as type 2 diabetes and cardiovascular disease. The accumulation of amyloid fibrils in these tissues can contribute to the development of insulin resistance and atherosclerosis, respectively.
Overall, plaques, amyloid are a complex and multifaceted area of research, with many open questions remaining about their formation, function, and clinical implications. Ongoing studies in this field may provide valuable insights into the pathogenesis of various diseases and ultimately lead to the development of novel therapeutic strategies for these conditions.
In conclusion, plaques, amyloid are a hallmark of several neurodegenerative diseases, including Alzheimer's disease, and have been associated with inflammation, oxidative stress, and neurodegeneration. The composition and structure of these plaques can vary depending on the underlying disease, and their presence is often linked to the progression of the condition. Furthermore, amyloid plaques have been implicated in other diseases such as type 2 diabetes and cardiovascular disease, highlighting their potential clinical significance beyond neurodegeneration. Ongoing research into the mechanisms of amyloid plaque formation and clearance may lead to the development of novel therapeutic strategies for these conditions.
There are several types of amyloidosis, each with different causes and symptoms. The most common types include:
1. Primary amyloidosis: This type is caused by the production of abnormal proteins in the bone marrow. It mainly affects older adults and can lead to symptoms such as fatigue, weight loss, and numbness or tingling in the hands and feet.
2. Secondary amyloidosis: This type is caused by other conditions, such as rheumatoid arthritis, tuberculosis, or inflammatory bowel disease. It can also be caused by long-term use of certain medications, such as antibiotics or chemotherapy.
3. Familial amyloid polyneuropathy: This type is inherited and affects the nerves in the body, leading to symptoms such as muscle weakness, numbness, and pain.
4. Localized amyloidosis: This type affects a specific area of the body, such as the tongue or the skin.
The symptoms of amyloidosis can vary depending on the organs affected and the severity of the condition. Some common symptoms include:
1. Fatigue
2. Weakness
3. Pain
4. Numbness or tingling in the hands and feet
5. Swelling in the legs, ankles, and feet
6. Difficulty with speech or swallowing
7. Seizures
8. Heart problems
9. Kidney failure
10. Liver failure
The diagnosis of amyloidosis is based on a combination of physical examination, medical history, laboratory tests, and imaging studies. Laboratory tests may include blood tests to measure the levels of certain proteins in the body, as well as biopsies to examine tissue samples under a microscope. Imaging studies, such as X-rays, CT scans, and MRI scans, may be used to evaluate the organs affected by the condition.
There is no cure for amyloidosis, but treatment can help manage the symptoms and slow the progression of the disease. Treatment options may include:
1. Medications to control symptoms such as pain, swelling, and heart problems
2. Chemotherapy to reduce the production of abnormal proteins
3. Autologous stem cell transplantation to replace damaged cells with healthy ones
4. Dialysis to remove excess fluids and waste products from the body
5. Nutritional support to ensure adequate nutrition and hydration
6. Physical therapy to maintain muscle strength and mobility
7. Supportive care to manage pain, improve quality of life, and reduce stress on the family.
In conclusion, amyloidosis is a complex and rare group of diseases that can affect multiple organs and systems in the body. Early diagnosis and treatment are essential to managing the symptoms and slowing the progression of the disease. It is important for patients with suspected amyloidosis to seek medical attention from a specialist, such as a hematologist or nephrologist, for proper evaluation and treatment.
The term "cerebral" refers to the brain, "amyloid" refers to the abnormal protein deposits, and "angiopathy" refers to the damage caused to the blood vessels. CAA is often associated with other conditions such as Alzheimer's disease, Down syndrome, and other forms of dementia.
CAA is a type of small vessel ischemic disease (SVID), which affects the smaller blood vessels in the brain. The exact cause of CAA is not yet fully understood, but it is thought to be related to a combination of genetic and environmental factors. There is currently no cure for CAA, but researchers are working to develop new treatments to slow its progression and manage its symptoms.
Some common symptoms of CAA include:
* Cognitive decline
* Seizures
* Stroke-like episodes
* Memory loss
* Confusion
* Difficulty with coordination and balance
If you suspect you or a loved one may be experiencing symptoms of CAA, it is important to speak with a healthcare professional for proper diagnosis and treatment. A thorough medical history and physical examination, along with imaging tests such as MRI or CT scans, can help confirm the presence of CAA.
While there is no cure for CAA, there are several treatment options available to manage its symptoms and slow its progression. These may include medications to control seizures, improve cognitive function, and reduce inflammation. In some cases, surgery or endovascular procedures may be necessary to repair or remove damaged blood vessels.
It is important to note that CAA is a complex condition, and its management requires a multidisciplinary approach involving neurologists, geriatricians, radiologists, and other healthcare professionals. With proper diagnosis and treatment, however, many individuals with CAA are able to lead active and fulfilling lives.
Amyloidosis can affect many different parts of the body, including the nervous system, the heart, the kidneys, the liver, and other organs. In the nervous system, amyloid accumulation can lead to various neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, prion diseases, and others.
Amyloid deposits in the nervous system can cause a range of symptoms including cognitive decline, memory loss, confusion, language impairment, and difficulty with coordination and movement. In addition, amyloid accumulation can lead to inflammation, oxidative stress, and excitotoxicity, which can further exacerbate neurodegeneration.
There are several types of amyloidosis that can affect the nervous system, including:
1. Alzheimer's disease: This is a progressive neurodegenerative disorder that is characterized by the accumulation of beta-amyloid peptides in the brain, leading to cognitive decline and memory loss.
2. Parkinson's disease: This is a neurodegenerative disorder that affects movement, balance, and coordination. It is characterized by the accumulation of alpha-synuclein protein in the brain.
3. Prion diseases: These are a group of rare, progressive neurodegenerative disorders that are caused by misfolded prion proteins. They can affect both the central and peripheral nervous systems.
4. Other forms of amyloidosis: There are several other forms of amyloidosis that can affect the nervous system, including primary lateral sclerosis, progressive supranuclear palsy, and corticobasal degeneration.
Amyloidosis can be diagnosed through a combination of clinical evaluation, imaging studies, and biopsy. Treatment options for amyloidosis vary depending on the underlying cause and severity of the disease. Some common treatments include:
1. Medications: There are several medications that can be used to treat amyloidosis, including cholinesterase inhibitors, dopamine agonists, and memantine.
2. Physical therapy: Physical therapy can help improve mobility, balance, and coordination in people with amyloidosis.
3. Speech therapy: Speech therapy can help improve communication and swallowing difficulties in people with amyloidosis.
4. Occupational therapy: Occupational therapy can help people with amyloidosis adapt to changes in their daily living activities and maintain their independence.
5. Surgery: In some cases, surgery may be necessary to relieve pressure on the brain or spinal cord caused by amyloid accumulation.
Currently, there is no cure for amyloidosis, but early diagnosis and treatment can help manage symptoms and improve quality of life. Research into new treatments and therapies is ongoing, including clinical trials exploring the use of stem cells, gene therapy, and immunotherapy to treat amyloidosis.
The symptoms of Alzheimer's disease can vary from person to person and may progress slowly over time. Early symptoms may include memory loss, confusion, and difficulty with problem-solving. As the disease progresses, individuals may experience language difficulties, visual hallucinations, and changes in mood and behavior.
There is currently no cure for Alzheimer's disease, but there are several medications and therapies that can help manage its symptoms and slow its progression. These include cholinesterase inhibitors, memantine, and non-pharmacological interventions such as cognitive training and behavioral therapy.
Alzheimer's disease is a significant public health concern, affecting an estimated 5.8 million Americans in 2020. It is the sixth leading cause of death in the United States, and its prevalence is expected to continue to increase as the population ages.
There is ongoing research into the causes and potential treatments for Alzheimer's disease, including studies into the role of inflammation, oxidative stress, and the immune system. Other areas of research include the development of biomarkers for early detection and the use of advanced imaging techniques to monitor progression of the disease.
Overall, Alzheimer's disease is a complex and multifactorial disorder that poses significant challenges for individuals, families, and healthcare systems. However, with ongoing research and advances in medical technology, there is hope for improving diagnosis and treatment options in the future.
Amyloidosis is a condition characterized by extracellular amyloid fibrils that are composed of insoluble, abnormal proteins. These fibrils accumulate in different parts of the body, leading to various symptoms and clinical manifestations depending on the type of protein involved.
There are several types of amyloidosis, including:
* Familial amyloid polyneuropathy (FAP): A rare inherited disorder caused by mutations in the transthyretin (TTR) gene, leading to progressive degeneration of the peripheral nerves.
* Familial amyloid cardiomyopathy: A rare inherited heart condition caused by mutations in the TTR gene, leading to progressive cardiac dysfunction and heart failure.
* Primary lateral sclerosis (PLS): A rare progressive neurodegenerative disorder characterized by weakness of the muscles of the limbs, face, and other parts of the body.
* Callidurin amyloidosis: A rare inherited disorder caused by mutations in the callidurin (CAL) gene, leading to progressive degeneration of the peripheral nerves.
The symptoms of these disorders vary depending on the type and severity of the condition, but may include muscle weakness, atrophy, and wasting; numbness or loss of sensation in the limbs; pain; cramping; and difficulty with walking, balance, and coordination. Diagnosis is typically made through a combination of clinical evaluation, imaging studies (such as MRI), and genetic testing. Treatment options are limited for these disorders and focus on managing symptoms and slowing disease progression.
The term 'familial' refers to the fact that CAA is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to cause the condition. This means that if one parent has the mutation, each child has a 50% chance of inheriting the mutated gene. The age of onset and severity of symptoms can vary widely among individuals with CAA, even within the same family.
There are several types of CAA, including:
1. Cerebral Amyloid Angiopathy, type 1 (CAA1): This is the most common form of CAA and is caused by mutations in the PROAPLIN1 gene.
2. Cerebral Amyloid Angiopathy, type 2 (CAA2): This form of CAA is less common and is caused by mutations in the PROAPLIN2 gene.
3. Cerebral Amyloid Angiopathy, type 3 (CAA3): This rare form of CAA is caused by mutations in the AGT gene.
There is currently no cure for CAA, but research is ongoing to develop new treatments and therapies to slow or halt the progression of the disease. Management of symptoms and prevention of complications are key components of care for individuals with CAA.
The different types of familial amyloidosis include:
1. Familial amyloid polyneuropathy (FAP): This is the most common type of familial amyloidosis and is characterized by the accumulation of amyloid fibers in the nerves, leading to progressive nerve damage and loss of sensation.
2. Familial amyloid cardiomyopathy (FAC): This type of amyloidosis affects the heart and is characterized by the accumulation of amyloid fibers in the heart muscle, leading to progressive heart failure.
3. Familial amyloidotic polyneuropathy (FAP): This type of amyloidosis affects the nerves and is characterized by the accumulation of amyloid fibers in the nerves, leading to progressive nerve damage and loss of sensation.
4. Primary amyloidosis (AL): This is a type of amyloidosis that is not inherited and is characterized by the accumulation of amyloid fibers in various organs and tissues throughout the body.
The symptoms of familial amyloidosis can vary depending on the specific type and the organs affected. Common symptoms include:
* Nerve damage and loss of sensation
* Heart failure
* Weakness and fatigue
* Pain
* Nausea and vomiting
* Diarrhea
* Constipation
* Weight loss
The diagnosis of familial amyloidosis is based on a combination of clinical findings, laboratory tests, and genetic analysis. Laboratory tests may include:
* Blood tests to measure the level of amyloid fibers in the blood
* Urine tests to measure the level of amyloid fibers in the urine
* Imaging studies such as X-rays, CT scans, or MRI scans to visualize the accumulation of amyloid fibers in the organs and tissues.
Treatment for familial amyloidosis is aimed at managing the symptoms and slowing the progression of the disease. Treatment options may include:
* Medications to manage pain, nausea, and vomiting
* Physical therapy to maintain muscle strength and mobility
* Dietary modifications to manage weight loss and malnutrition
* Heart failure medications to manage heart failure
* Kidney dialysis or transplantation to manage kidney failure
* Stem cell transplantation to slow the progression of the disease.
The prognosis for familial amyloidosis is generally poor, and the disease can be fatal within a few years after diagnosis. However, with early diagnosis and appropriate treatment, some people with familial amyloidosis may experience a better quality of life and longer survival time. It is important to note that there is currently no cure for familial amyloidosis, and research is ongoing to develop new and more effective treatments for the disease.
1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.
2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.
3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.
4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.
5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.
6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.
7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.
8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.
9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.
10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.
The disorder is caused by an abnormal expansion of a CAG repeat in the inclusions in certain neurons in the brain, leading to a deficiency of the enzyme glucocerebrosidase. This results in the accumulation of a fatty substance called glucocerebroside in the brain, which leads to progressive damage to brain cells and loss of cognitive and motor functions.
Symptoms of GSSD typically begin in adulthood and can include difficulty with speech, language, and cognition, as well as problems with coordination, balance, and movement. As the disease progresses, patients may experience seizures, vision loss, and ultimately, dementia and death.
GSSD is a rare disorder that affects approximately one in a million people worldwide. It is usually inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the abnormal gene (one from each parent) to develop the disease. There is currently no cure for GSSD, and treatment is focused on managing symptoms and slowing the progression of the disease.
Some common examples of neurodegenerative diseases include:
1. Alzheimer's disease: A progressive loss of cognitive function, memory, and thinking skills that is the most common form of dementia.
2. Parkinson's disease: A disorder that affects movement, balance, and coordination, causing tremors, rigidity, and difficulty with walking.
3. Huntington's disease: An inherited condition that causes progressive loss of cognitive, motor, and psychiatric functions.
4. Amyotrophic lateral sclerosis (ALS): A disease that affects the nerve cells responsible for controlling voluntary muscle movement, leading to muscle weakness, paralysis, and eventually death.
5. Prion diseases: A group of rare and fatal disorders caused by misfolded proteins in the brain, leading to neurodegeneration and death.
6. Creutzfeldt-Jakob disease: A rare, degenerative, and fatal brain disorder caused by an abnormal form of a protein called a prion.
7. Frontotemporal dementia: A group of diseases that affect the front and temporal lobes of the brain, leading to changes in personality, behavior, and language.
Neurodegenerative diseases can be caused by a variety of factors, including genetics, age, lifestyle, and environmental factors. They are typically diagnosed through a combination of medical history, physical examination, laboratory tests, and imaging studies. Treatment options for neurodegenerative diseases vary depending on the specific condition and its underlying causes, but may include medications, therapy, and lifestyle changes.
Preventing or slowing the progression of neurodegenerative diseases is a major focus of current research, with various potential therapeutic strategies being explored, such as:
1. Stem cell therapies: Using stem cells to replace damaged neurons and restore brain function.
2. Gene therapies: Replacing or editing genes that are linked to neurodegenerative diseases.
3. Small molecule therapies: Developing small molecules that can slow or prevent the progression of neurodegenerative diseases.
4. Immunotherapies: Harnessing the immune system to combat neurodegenerative diseases.
5. Lifestyle interventions: Promoting healthy lifestyle choices, such as regular exercise and a balanced diet, to reduce the risk of developing neurodegenerative diseases.
In conclusion, neurodegenerative diseases are a complex and diverse group of disorders that can have a profound impact on individuals and society. While there is currently no cure for these conditions, research is providing new insights into their causes and potential treatments. By continuing to invest in research and developing innovative therapeutic strategies, we can work towards improving the lives of those affected by neurodegenerative diseases and ultimately finding a cure.
The term "acute-phase" describes the rapid onset and short duration of this reaction, which typically lasts for hours to days before resolving as the body's inflammatory response subsides. APR is characterized by a series of molecular events that result in altered expression of genes involved in inflammation, immune response, and tissue repair.
Some key components of an acute-phase reaction include:
1. Cytokine production: Cytokines are signaling molecules released by immune cells, such as white blood cells, that coordinate the immune response. During an APR, cytokine levels increase, triggering a cascade of downstream effects.
2. Leukocyte trafficking: White blood cells migrate towards sites of inflammation or infection, where they phagocytose (engulf and digest) pathogens and cellular debris. This process helps to limit the spread of infection and initiate tissue repair.
3. Coagulation cascade: The APR triggers a complex series of events involving blood coagulation factors, leading to the formation of blood clots and preventing excessive bleeding.
4. Anti-inflammatory response: As the APR progresses, anti-inflammatory cytokines, such as interleukin-10 (IL-10), are produced to dampen the inflammatory response and promote tissue repair.
5. Cellular proliferation: To replace damaged cells and tissues, the APR stimulates cellular proliferation and tissue regeneration.
6. Nutrient mobilization: The APR enhances nutrient uptake and utilization by immune cells, allowing them to mount an effective response to the stress.
7. Hormonal changes: The APR is accompanied by changes in hormone levels, such as the increase in corticotropin-releasing factor (CRF) and cortisol, which help to mobilize energy resources and regulate metabolism.
8. Immune tolerance: The APR helps to establish immune tolerance, preventing excessive or inappropriate immune responses that can lead to autoimmune diseases or allergies.
9. Tissue remodeling: The APR stimulates the remodeling of damaged tissues, allowing for the restoration of normal tissue function.
10. Memory formation: The APR sets the stage for the formation of immunological memory, which enables the immune system to mount a more effective response to future infections or stressors.
The most common form of prion disease in humans is Creutzfeldt-Jakob disease (CJD), which typically affects people over the age of 60. Other forms of prion diseases include variably protease-sensitive prionopathy (VPSPr) and fatal familial insomnia (FFI).
The symptoms of prion diseases vary depending on the specific form of the disease, but they often include:
* Cognitive decline and memory loss
* Coordination and balance problems
* Slurred speech and difficulty with communication
* Difficulty with movement and muscle control
* Depression and anxiety
* Sleep disturbances
* Loss of appetite and weight loss
Prion diseases are diagnosed through a combination of clinical evaluation, imaging studies, and laboratory tests. There is no cure for prion diseases, and treatment is focused on managing symptoms and supporting the patient's quality of life.
Prevention of prion diseases is important, as there is no effective treatment once the disease has developed. Measures to prevent the spread of prion diseases include:
* Implementing strict infection control measures in healthcare settings, such as wearing personal protective equipment and sterilizing equipment and surfaces
* Avoiding exposure to infected tissues and fluids, such as through medical procedures or consumption of contaminated beef products
* Monitoring and testing individuals who have been exposed to prion diseases, such as healthcare workers and family members of affected individuals
* Developing and distributing vaccines and other treatments to prevent and treat prion diseases.
Overall, prion diseases are a group of devastating neurodegenerative disorders that can have a significant impact on the lives of those affected. Understanding the causes, symptoms, diagnosis, treatment, and prevention of these diseases is crucial for improving outcomes and supporting individuals and families affected by prion diseases.
Gliosis is made up of glial cells, which are non-neuronal cells that provide support and protection to neurons. When neural tissue is damaged, glial cells proliferate and form a scar-like tissue to fill in the gap and repair the damage. This scar tissue can be made up of astrocytes, oligodendrocytes, or microglia, depending on the type of injury and the location of the damage.
Gliosis can have both beneficial and harmful effects on the brain. On one hand, it can help to prevent further damage by providing a physical barrier against invading substances and protecting the surrounding neural tissue. It can also promote healing by bringing in immune cells and growth factors that aid in the repair process.
On the other hand, gliosis can also have negative effects on brain function. The scar tissue can disrupt normal communication between neurons, leading to impaired cognitive and motor function. In addition, if the scar tissue is too extensive or severe, it can compress or displaces surrounding neural tissue, leading to long-term neurological deficits or even death.
There are several ways to diagnose gliosis, including magnetic resonance imaging (MRI), positron emission tomography (PET), and histopathology. Treatment options for gliosis depend on the underlying cause of the condition and can include medications, surgery, or a combination of both.
In summary, gliosis is a type of scar tissue that forms in the brain and spinal cord as a result of damage to neural tissue. It can have both beneficial and harmful effects on brain function, and diagnosis and treatment options vary depending on the underlying cause of the condition.
Amyloid
Amyloid (journal)
Amyloid beta
Amyloid purpura
Amyloid cardiomyopathy
Amyloid (disambiguation)
Amyloid (mycology)
Amyloid plaques
Cerebral amyloid angiopathy
Familial amyloid polyneuropathy
Familial amyloid neuropathy
Serum amyloid A1
Familial amyloid cardiomyopathy
Serum amyloid A
Wild-type transthyretin amyloid
Amyloid-related imaging abnormalities
Amyloid-beta precursor protein
Serum amyloid P component
Amyloid-beta precursor protein secretase
Hereditary cystatin C amyloid angiopathy
LECT2
Electrochemical skin conductance
Bence Jones protein
Familial renal amyloidosis
SAA4
Edward C. Franklin
Monoclonal antibody therapy
Serum free light-chain measurement
Ardalan-Shoja-Kiuru syndrome
Familial British dementia
Cerebral amyloid angiopathy: MedlinePlus Medical Encyclopedia
A primer of amyloid nomenclature
NIMH » 1.6 Radiotracers for β-amyloid
Gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils | Scientific Reports
Partial Amyloid Beta Inhibition Improves Memory in Alzheimer's
Amyloid Deposition - Degenerative Lesions of the Liver
Amyloid Hypothesis For Alzheimer's In Doubt After Lilly's Drug Failure : Shots - Health News : NPR
Study of AV-1959, an Amyloid Beta Vaccine - Full Text View - ClinicalTrials.gov
Beta-amyloid X-40 peptides | AnaSpec
Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G(o) | ALZFORUM
Recombinant Anti-Amyloid Precursor Protein antibody [EPR5118-34] KO Tested (ab126732)
Amyloidosis: Definition of Amyloid and Amyloidosis, Classification Systems, Systemic Amyloidoses
Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4)
A Broader Role for Amyloids | National Institutes of Health (NIH)
Difference Between Amyloid and Tau | Difference Between
tsai-martorell-amyloid-cortex 3.22.19 - Americans for Medical Progress
Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
talks.cam : Heterotypic Amyloid Interactions and their Impact on Amyloid Assembly
Investigations of the effects of amyloid-beta peptide on hSlo1.1 | Molecular Devices
Protocol - Immunohistochemistry Protocol for Beta Amyloid Products using USA Detection Kit
Four Immunotherapies Now Proven to Reduce Amyloid-β in the Aging Brain - Fight Aging!
APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge | bioRxiv
Mechanisms of Amyloidogenesis of Beta-Amyloid Peptide | BrightFocus Foundation
amyloid beta elisa - Argentine Bioethics Association
Tale of amyloid filaments in neurodegenerative diseases
Associations of Dietary Protein and Fiber Intake with Brain and Blood Amyloid-β. | Journal of Alzheimer's Disease
P-Glycoprotein Efflux and Other Factors Limit Brain Amyloid β Reduction by β-Site Amyloid Precursor Protein-Cleaving Enzyme 1...
Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection | eLife
Protein27
- People with CAA have deposits of amyloid protein in the walls of blood vessels in the brain. (medlineplus.gov)
- All amyloid types are today preferably named by their major fibril protein. (nih.gov)
- Essentially, under this hypothesis over-production of the peptides Aβ 40 and, especially Aβ 42 , from amyloid precursor protein with eventual deposition of amyloid (Aβ) plaques is the mechanism of pathogenesis. (nih.gov)
- But the frustration brought by this particular failure could signal a shift in Alzheimer's research - a shift away from targeting accumulations of so-called amyloid protein in the brain, long considered by many in the field to be the crux of Alzheimer's pathology. (npr.org)
- Ever since Dr. George G. Glenner's 1984 discovery that amyloid is the main component of the plaques that riddle the Alzheimer's-afflicted brain, it has been assumed that the protein somehow contributes to the disorder - that it jams up cellular machinery, rendering neurons unable to effectively communicate, to form new memories, to remember where the keys are. (npr.org)
- A different type of investigational medication, so-called BACE inhibitors, prevent amyloid formation in the first place, by neutralizing an enzyme that cuts away amyloid from a larger protein. (npr.org)
- Sequential proteolytic cleavage of the Amyloid Precursor Protein (APP) by secretases (α, β, γ) generates beta-Amyloid peptide fragments. (anaspec.com)
- Nishimoto I, Okamoto T, Matsuura Y, Takahashi S, Murayama Y, Ogata E . Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G(o) . (alzforum.org)
- Amyloid fibrils are protein polymers comprising identical monomer units (homopolymers). (medscape.com)
- All types of amyloid consist of one major fibrillar protein that defines the type of amyloid. (medscape.com)
- Polymorphisms that slightly vary native peptides or inflammatory processes set the stage for abnormal protein folding and amyloid fibril deposition. (medscape.com)
- The amyloidoses are referred to with a capital A (for amyloid) followed by an abbreviation for the fibril protein. (medscape.com)
- Synthetic peptide within Human Amyloid Precursor Protein aa 50-150 (extracellular). (abcam.com)
- This study will test whether an investigational drug, solanezumab, can slow the progression of memory problems associated with amyloid, a protein that forms plaques in the brains of people with Alzheimer disease. (nih.gov)
- They are made of highly organized protein arrangements called β-sheets that stack perpendicularly along the axis of the amyloid fiber. (nih.gov)
- With funding from NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the researchers explored whether protein hormones could form amyloids. (nih.gov)
- Abstract: Heterotypic amyloid interactions between related protein sequences have been observed in functional and disease amyloids. (cam.ac.uk)
- Associations of Dietary Protein and Fiber Intake with Brain and Blood Amyloid-β. (j-alz.com)
- Based on this hypothesis, β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) inhibitors are an attractive therapeutic approach for AD because cleavage of the APP by BACE1 is required to form Aβ. (aspetjournals.org)
- The trafficking and metabolism of amyloid precursor protein (APP). (nih.gov)
- What can PAT1 do for amyloid precursor protein? (nih.gov)
- Thus, structurally distinct amyloids composed of the same protein were differentially sensitive to the anti-amyloid activity of DnaJB6 both in vitro and in vivo. (nih.gov)
- In a stroke of luck, one of Yankner's insertions encoded a precursor to a protein called amyloid. (nih.gov)
- These patients were identified by the presence of amyloid or tau protein in PET measurements. (medscape.com)
- The Laboratory of Protein Conformation and Dynamics integrates complementary biophysical and biochemical techniques to understand the molecular mechanisms of amyloid formation. (nih.gov)
- Dr. Lee focuses her research efforts on studying changes in protein conformation and dynamics important for the mechanisms by which amyloid structures assemble under normal and pathological conditions. (nih.gov)
- To determine the critical features guiding amyloid formation, Dr. Lee is characterizing how individual amino acid residues affect protein-protein interaction during the amyloid assembly process. (nih.gov)
Plaques12
- Diseased brain tissue from an Alzheimer's patient showing amyloid plaques (in blue) located in the gray matter of the brain. (npr.org)
- Biogen's aducanumab, another experimental drug that's far along in clinical testing , binds to and clears amyloid that is already ensnared in plaques. (npr.org)
- Earlier this year the FDA granted aducanumab fast-track status after results from a small, early-stage study suggested that it reduces amyloid plaques and slows cognitive decline in people with very early stage disease. (npr.org)
- Beta-Amyloid 1-42 forms a major component of amyloid plaques in neurons of Alzheimer's disease (AD) brains, while beta-Amyloid 1-40 is taken as a negative control of beta-Amyloid 1-42 in most studies. (anaspec.com)
- Pyroglutamate-modified (Pyr) beta-Amyloid 3-40 and 11-40 have been described as major compounds in the senile AD plaques. (anaspec.com)
- These dense plaques are made of proteins that are normally found in the body but have misfolded to form amyloids. (nih.gov)
- Beta amyloids chunks become stuck to one another and end up as hardened deposited plaques in the brain cell connections. (differencebetween.net)
- The disease was classically characterized by widespread deposition of insoluble amyloid-beta (Aβ) plaques throughout the cortex, leading to synaptic dysfunction and neuronal loss. (moleculardevices.com)
- In Aubrey de Grey's August bi monthly review of Theses relevant to combating aging he highlighted a paper suggesting that perhaps amyloid beta plaques don't actually cause damage in Alzheimers, it is the fact that they rupture cellular endosomes that results in cell death. (fightaging.org)
- The identification of amyloid-rich plaques has long been a diagnostic tool for pathologists investigating Alzheimer's disease (AD). (nih.gov)
- The APOE -Aß interaction regulates Aß aggregation and clearance and therefore directly influences the development of amyloid plaques , congophilic amyloid angiopathy and subsequent tau related pathology . (bvsalud.org)
- Injection of NEP-expressing lentivirus, but not inactive NEP-expressing lentivirus, GFP-expressing lentivirus, or vehicle, into the hippocampus of 12-20-mo-old hAPP transgenic mice led to an approx 50% reduction in the number of amyloid plaques. (nih.gov)
Peptide3
- Functional amyloids play a beneficial role in a variety of physiologic processes (eg, long-term memory formation, gradual release of stored peptide hormones). (medscape.com)
- NIEHS scientists discovered that beta-amyloid peptide, found in patients with Alzheimer's disease, can disrupt brain signals that may contribute to the memory loss associated with Alzheimer's disease. (nih.gov)
- 2001. Beta-amyloid(1-42) peptide directly modulates nicotinic receptors in the rat hippocampal slice. (nih.gov)
Proteins21
- Cerebral amyloid angiopathy (CAA) is a condition in which proteins called amyloid build up on the walls of the arteries in the brain. (medlineplus.gov)
- Amyloidosis results from the accumulation of pathogenic amyloids-most of which are aggregates of misfolded proteins-in a variety of tissues. (medscape.com)
- [ 5 ] Only 10% of amyloidosis deposits consist of components such as glycosaminoglycans (GAGs), apolipoprotein-E (apoE), and serum amyloid P-component (SAP), while nearly 90% of the deposits consist of amyloid fibrils that are formed by the aggregation of misfolded proteins. (medscape.com)
- [ 6 ] In humans, about 23 different unrelated proteins are known to form amyloid fibrils in vivo. (medscape.com)
- Amyloids are actually defined by their structure, not the specific proteins that form them. (nih.gov)
- Beta amyloid (amyloid-β) and tau are both proteins synonymous with Alzheimer's Disease. (differencebetween.net)
- Amyloid proteins are commonly known in the medical world for their contribution to Alzheimer's disease . (differencebetween.net)
- Beta amyloids are parented by amyloid precursor proteins, commonly known as APP. (differencebetween.net)
- A number of professionals say that the beta amyloid proteins allow brain cells to send signals. (differencebetween.net)
- These enzymes cut APP up into chunks of proteins, beta amyloids, which is not able to be metabolized by the brain. (differencebetween.net)
- Both proteins (amyloid and tau) become stuck in clumps when their processes are disrupted. (differencebetween.net)
- We find that these heterotypic amyloid interactions can result in the subcellular mislocalisation of these proteins. (cam.ac.uk)
- Our findings suggest a structural mechanism by which the proteomic background can modulate the aggregation propensity of amyloidogenic proteins and we discuss how such sequence specific proteostatic perturbations could contribute to the selective cellular susceptibility of amyloid disease progression. (cam.ac.uk)
- Serum amyloid A (SAA) proteins are strongly induced in the liver by systemic infection and in the intestine by bacterial colonization, but their exact functions remain unclear. (elifesciences.org)
- It had been suggested that Serum Amyloid A (SAA) proteins, a family of proteins made by some liver and intestinal cells, could be involved in the response to infection, because these proteins' levels increase during infection. (elifesciences.org)
- Although the roles of APP, the presenilins, and other molecules implicated in AD still require significant investigation, the characterization of genes and proteins that are linked to amyloid plaque formation may help build a picture of the events that lead to AD. (nih.gov)
- The person in the position will perform experiments with human brain samples and transgenic mice and amyloid fibrils and oligomers formed from synthetic and recombinant purified proteins under the direction of Dr. Charles Glabe. (uci.edu)
- Experience working with amyloids and insoluble proteins and proteomic analysis are preferred. (uci.edu)
- Yeast prions [URE3] and [PSI] propagate as amyloid forms of Ure2 and Sup35 proteins, respectively. (nih.gov)
- Aggregation of proteins into amyloid structures is a hallmark of human diseases such as Alzheimer's, Parkinson's, and Hungtington's. (nih.gov)
- To begin to understand these differences, Dr. Lee is currently investigating the mechanisms of amyloid formation for two human proteins: α-synuclein, which is localized to nerve terminals and associated with Parkinson's disease, and Pmel17, which serves as structural scaffolding for melanin deposition in skin and eyes. (nih.gov)
Alzheimer's Disease7
- Phase 1 clinical trial of AV-1959 amyloid-β vaccine for Alzheimer's disease (AD). (clinicaltrials.gov)
- A Phase I, Randomized, Double-Blind Study to Evaluate Safety and Tolerability of Amyloid-β Vaccine, AV-1959D, in Patients With Early Alzheimer's Disease. (clinicaltrials.gov)
- Immunotherapies that target aggregation of amyloid-β in order to treat Alzheimer's disease have a long and expensive history of failure. (fightaging.org)
- The present consensus on Alzheimer's disease is that amyloid-β accumulation is an early phase, damaging yes, but nowhere near as damaging as the tau aggregation that occurs later on. (fightaging.org)
- It clinched the case that these antibodies can mop up brain amyloid, bringing many people with early symptomatic Alzheimer's disease (AD) below the threshold for amyloid positivity. (fightaging.org)
- Those experiments and later ones from Yankner's own lab showed definitively that high concentrations of amyloid, as found in the brains of people with Alzheimer's disease, are toxic to neural cells [1]. (nih.gov)
- In summary, this means that at present we have two monoclonal antibodies against beta-amyloid that showed efficacy in the early stages of Alzheimer's disease. (medscape.com)
Fibrils6
- In these experiments, one of the methods used to track the existence or formation of amyloids is an amyloidophilic dye molecule-thioflavin-T (ThT), which fluorescence emission intensity increases significantly when it binds to the beta-sheet grooves on the surface of amyloid fibrils 23 . (nature.com)
- Amyloidosis is a clinical disorder caused by extracellular and/or intracellular deposition of insoluble abnormal amyloid fibrils that alter the normal function of tissues. (medscape.com)
- The modern era of amyloidosis classification began in the late 1960s with the development of methods to solubilize amyloid fibrils. (medscape.com)
- Along with tafamidis, the first approved therapy for ATTR-cardiomyopathy (CM), several other agents are in late-stage clinical development for ATTR-CM. TTR-stabilizing and -silencing agents with various mechanisms target TTR, preventing disaggregation of tetrameric TTR, and subsequent misfolding of TTR and formation of amyloid fibrils in the myocardium. (nih.gov)
- This NIH-funded project aims at developing methods for the purification and preparation of homogeneous amyloid oligomers and fibrils of different structural polymorphs and tools for studying amyloid polymorphism in vitro and in vivo. (uci.edu)
- Interestingly, amyloid fibrils can also serve essential biological roles in organisms ranging from bacteria to humans. (nih.gov)
Aggregation3
- Pyro-Glu modified beta-Amyloid forms are more resistant to degradation, show higher toxicity and have increased aggregation propensity compared to the non-modified beta-Amyloid equivalent. (anaspec.com)
- The researcher also will work on the seeded aggregation and replication of these amyloids isolated from human brain. (uci.edu)
- Ultimately, Dr. Lee wants to understand the mechanisms of amyloid aggregation and function at a detailed level in the context of the multiple cellular compartments with which they interact. (nih.gov)
Form amyloid2
- The prion domain readily forms amyloid in vitro and, when mixed with the native full-length Ure2p, also induces the latter to form amyloid. (nih.gov)
- Moreover, many polypeptides with widely varying amino acid sequences and folded states can form amyloid in vitro, implying common formation pathways. (nih.gov)
Pathology4
- As the beta-amyloid is central to AD pathology, beta-amyloid is being pursued as a therapeutic target, including through passive immunotherapy against beta-amyloid. (nih.gov)
- She would like to not only describe the self-assembly process and its critical features, but also determine points of intervention in which amyloid assembly is linked to pathology. (nih.gov)
- β-Amyloid (Aβ) pathology is common in patients with probable dementia with Lewy bodies (DLB). (nih.gov)
- Confirm the presence of amyloid beta pathology prior to initiating treatment. (nih.gov)
Cerebral amyloid an4
- Emerging concepts in sporadic cerebral amyloid angiopathy. (medlineplus.gov)
- Greenberg SM, Charidimou A. Diagnosis of cerebral amyloid angiopathy: evolution of the Boston criteria. (medlineplus.gov)
- Although cortical superficial siderosis has many possible causes, it is emerging as a key feature of cerebral amyloid angiopathy, a common and important age-related cerebral small vessel disorder leading to intracerebral haemorrhage and dementia. (eur.nl)
- In this review we focus on recent developments in neuroimaging and detection, aetiology, prevalence, pathophysiology and clinical significance of cortical superficial siderosis, with a particular emphasis on cerebral amyloid angiopathy. (eur.nl)
Amyloidosis3
- Amyloid deposits in the glomeruli of the kidney are usually the cause of death in animals that die with amyloidosis. (nih.gov)
- Recent efforts in basic science have elucidated the pathobiology of amyloid transthyretin (ATTR) amyloidosis, leading to the development of the first generation of transthyretin (TTR)-targeted therapies for this disease. (nih.gov)
- Anti-amyloid treatments represent another strategy for treating patients with advanced ATTR amyloidosis. (nih.gov)
Types of amyloid1
- The hypothesis to be examined is that different types of amyloid accumulate in different phenotypic variants of disease. (uci.edu)
Deposition of amyloid1
- In the esophagus and small intestine, the disease appears to begin as a deposition of amyloid in the submucosa. (nih.gov)
Dementia3
- 76 Radiotracers are sought for imaging Aβ preceding clinical signs of dementia, although we have argued that such radiotracers will eventually have more utility for investigating pathophysiology and the validity of the β-amyloid cascade hypothesis. (nih.gov)
- Further, Alzheimer's patients also tend to have other forms of neurodegeneration , such as vascular dementia , that are unlikely to be greatly affected by amyloid-β clearance. (fightaging.org)
- Anti-Beta-Amyloid Passive Immunotherapy for Alzheimer’s Dementia and Amyloid Related Imaging Abnormalities (ARIA): What’s Next? (nih.gov)
Brain11
- Like many other failed medications for symptomatic Alzheimer's, solanezumab works by attacking amyloid in the brain. (npr.org)
- By the time symptoms of Alzheimer's arise, the brain is already speckled with amyloid. (npr.org)
- All volunteers will undergo a positron emission tomography (PET) scan to be determine their brain amyloid levels. (nih.gov)
- Amyloid can also cause problems beyond the brain. (nih.gov)
- The amyloids produced inside the brain are processed by the alpha secretase enzyme. (differencebetween.net)
- When processes involving amyloids (beta amyloid or APP) go rogue, brain cell connections and guidance are negatively impacted. (differencebetween.net)
- These studies showed that all three BACE1 inhibitors decreased brain Aβ1-40 in P-gp KO mice, demonstrating that P-gp is a major limitation for development of BACE1 inhibitors to test the amyloid hypothesis. (aspetjournals.org)
- This funding opportunity announcement (FOA) solicits applications designed to increase understanding of cellular and molecular mechanisms that can be targeted to protect the blood-brain barrier (BBB), and thus brain blood vessels, during therapeutic interventions that target beta-amyloid. (nih.gov)
- This includes applications that promote the discovery of cellular and molecular mechanisms that underlie brain blood vessels responses to passive anti-beta-amyloid immunotherapy that result in amyloid-related imaging abnormalities (ARIA) and other potentially adverse cerebrovascular responses. (nih.gov)
- Because of the translational potential of passive anti-beta-amyloid immunotherapy on the ADRD disease processes, understanding the effect of this therapy on the blood-brain barrier and brain blood vessels in the intact living brain is critically important. (nih.gov)
- Imaging brain amyloid : progress and promise / Chester A. Mathis. (nih.gov)
Deposits4
- Those people did have amyloid deposits visible with positron emission tomography imaging. (npr.org)
- These trials also suggest that the best chance for a significant effect on cognition is likely to be treating asymptomatic people with amyloid deposits on imaging. (npr.org)
- Whenever present, amyloid deposits should be diagnosed as "amyloid" and graded based on the extent of the amyloid deposits. (nih.gov)
- Various descriptive classification systems were proposed based on the organ distribution of amyloid deposits and clinical findings. (medscape.com)
ApoE2
- APOE-amyloid interaction: Therapeutic targets. (bvsalud.org)
- The interaction between APOE and amyloid ß (Aß) plays a key role in AD pathogenesis . (bvsalud.org)
Antibody2
- Solanezumab, an antibody, works by attacking amyloid floating in cerebrospinal fluid. (npr.org)
- We had a positive trial with an antibody against beta-amyloid at the beginning of this year, called lecanemab, which is now approved in the United States. (medscape.com)
Clinical5
- Such a nomenclature, biochemically based, has been used for several years but the current literature is still mixed up with many clinical and histochemically based designations from the time when amyloid in general was poorly understood. (nih.gov)
- The search for a potential anti-amyloid drug has led to the discovery of hundreds of compounds, none of which have passed all clinical trials. (nature.com)
- Yet, Burke adds, if these trials don't show a significant clinical benefit, the focus on amyloid will likely end. (npr.org)
- Several of the antibodies are looking good at removing amyloid, but the clinical efficacy still needs to be demonstrated. (fightaging.org)
- Amyloid Related Imaging Abnormalities (ARIA): Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI. (nih.gov)
Hypothesis1
- The β-amyloid cascade hypothesis 75 has been central to the development of treatment strategies over recent years. (nih.gov)
Transthyretin1
- Transthyretin amyloid cardiomyopathy, also known as ATTR-CM, is a type of cardiomyopathy which is underdiagnosed and potentially fatal. (singhealth.com.sg)
Functional2
Monoclonal2
- Monoclonal antibodies directed against aggregated forms of beta amyloid, including LEQEMBI, can cause amyloid related imaging abnormalities (ARIA), characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). ARIA is usually asymptomatic, although rarely serious and life-threatening events can occur. (nih.gov)
- Monoclonal antibodies directed against aggregated forms of beta amyloid, including LEQEMBI, can cause amyloid related imaging abnormalities (ARIA), characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). Incidence and timing of ARIA vary among treatments. (nih.gov)
Conformation1
- PSI] prions can propagate as weak or strong variants, which differ only in the structural conformation of their amyloid cores. (nih.gov)
Blood vessels1
- Amyloid deposition around blood vessels in the portal areas. (nih.gov)
Ure22
- We found that the amyloid of Ure2p consists of a beta-sheet core region (Ure2 residues 1-65) (Fig. 2), a C-terminal domain similar in structure to glutathione-S-transferases (Ure2 residues 95-354), and a flexible tether connecting these two regions (Ure2 residues 66-94). (nih.gov)
- In Ure2 amyloid, monomers are connected by interactions between the N-terminal domains. (nih.gov)
Accumulation2
- Amyloid appears as an amorphous, eosinophilic, hyaline, extracellular substance (Figure 1, arrow) that, with progressive accumulation, results in pressure atrophy of adjacent cel s and tissue. (nih.gov)
- But still: researchers claimed that two years of treatment with high-dose gantenerumab essentially resets a person's trajectory of amyloid accumulation. (fightaging.org)
Biochemical2
- The increasing knowledge of the exact biochemical nature of the localized and systemic amyloid disorders has made a logical and easily understood nomenclature absolutely necessary. (nih.gov)
- Dr. Lee's laboratory integrates a variety of biophysical and biochemical techniques to understand the molecular mechanisms of amyloid formation. (nih.gov)
Characterized by widespread1
- E4 microglia display increased Hif1α expression, a disrupted TCA cycle, and are inherently pro-glycolytic, while spatial transcriptomics and MALDI mass spectrometry imaging highlight an E4-specific response to amyloid that is characterized by widespread alterations in lipid metabolism. (biorxiv.org)
Interestingly1
- Interestingly enough, amyloids are not harmful until things go wrong. (differencebetween.net)
Amorphous1
- Amorphous eosinophilic interstitial amyloid observed on a renal biopsy. (medscape.com)
Eosinophilic1
- There is a cellular, eosinophilic material (amyloid) in the submucosa of the esophagus (arrow). (nih.gov)
Serum1
- Serum Amyloid A: Where next for this biomarker? (avacta.com)
Mechanisms1
- Therefore, this FOA invites basic disease-related molecular mechanisms applications that use age-appropriate beta-amyloid animal models to understand genetic, cellular, and molecular factors that result in adverse responses at and/or proximal to the BBB due to passive anti-beta-amyloid immunotherapy. (nih.gov)
Inhibiting an enzyme1
- New York University researchers, after a successful animal study, suggest that partially inhibiting an enzyme that initiates the release of amyloid beta may help improve memory dysfunction. (medindia.net)
Recombinant3
- This study led to the high-resolution structure determination 76 structures of recombinant tau filaments assembled in vitro, providing a new database for the greater amyloid field. (labroots.com)
- We showed that amyloid of recombinant Ure2p is infectious for yeast cells, infecting them with the [URE3] prion. (nih.gov)
- Cells infected with amyloid of recombinant Ure2p carry any of a large number of heritable prion variants. (nih.gov)
Neurodegenerative1
- Gallic acid has been shown to both modulate factors leading to the onset of neurodegenerative disorders, as well as directly inhibit amyloid formation. (nature.com)
Beta7
- N-terminally truncated beta-Amyloid 3-40 ad 11-40 , both having a Glu as first residue, are subjected to pyro-glutamination. (anaspec.com)
- [ 2 ] Many classic eponymic diseases were later found to be related to a diverse array of misfolded polypeptides (amyloid) that contain the common beta-pleated sheet architecture. (medscape.com)
- Other professionals are of the opinion that the beta amyloids are important in early development stages and guide cells on how to attach to each other. (differencebetween.net)
- Tau is better understood by scientists in comparison to the nature of beta amyloids and disease. (differencebetween.net)
- Protocol can be used for Beta Amyloid products that list "IHC" as an application on the datasheet ( e.g . clones 4G8, 6E10, etc). (biolegend.com)
- Mutations in the presenilins increase the production of beta-amyloid, suggesting that they influence the metabolism of APP in some way. (nih.gov)
- Human chaperone DnaJB6, an Hsp70 co-chaperone whose defects cause myopathies, protects cells from polyglutamine toxicity and prevents purified polyglutamine and A-beta peptides from forming amyloid. (nih.gov)
Variants1
- In line with its anti-prion effects, DnaJB6 prevented purified Sup35 from forming amyloids at 37 °C, which produce predominantly weak [PSI] variants when used to infect yeast, but not at 4 °C, which produces mostly strong [PSI] variants. (nih.gov)
Therapies1
- The challenge for amyloid-β clearance therapies is now to show benefits in patients, and there are good reasons to believe that this will be challenging in the late disease state. (fightaging.org)
Congo3
- Special stains such as Congo red can be used to confirm that the material is amyloid. (nih.gov)
- Congo red stains amyloid orange to orange red and under polarized light imparts a characteristic light green birefringence that is often referred to as apple green. (nih.gov)
- Congo red staining of a cardiac biopsy specimen containing amyloid, viewed under polarized light. (medscape.com)
Disorders2
Disease1
- It may not be amyloids themselves that cause disease, but rather conditions that lead too much amyloid to form in the wrong places. (nih.gov)
Degradation1
- Or is the formation and degradation of amyloids regulated more efficiently in healthy cells? (nih.gov)
Treatments1
- The tide finally seems to be turning, however, with the advent of several treatments that can reduce amyloid-β levels without resulting in an unacceptable level of risk for the patients. (fightaging.org)
Cells1
- Since amyloids are thought to be toxic to neuronal cells, the researchers tested whether the ones they'd created were toxic to a neuronal cell line in the laboratory. (nih.gov)
Progression1
- Amyloid β (Aβ) peptides are hypothesized to cause the initiation and progression of AD based on pathologic data from AD patients, genetic analysis of mutations that cause early onset forms of AD, and preclinical studies. (aspetjournals.org)
Experiments1
- These experiments provide evidence that secretory granules contain amyloids, and that amyloids help the body store and release hormones. (nih.gov)
Drugs1
- Seizures, also called amyloid spells, may be treated with anti-seizure drugs. (medlineplus.gov)