Amyloid beta (Aβ or Abeta) denotes peptides of 36-43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. (wikipedia.org)
Aβ is the main component of amyloid plaques, extracellular deposits found in the brains of people with Alzheimer's disease. (wikipedia.org)
Research suggests that soluble oligomeric forms of the amyloid beta may be causative agents in the development of Alzheimer's disease. (wikipedia.org)
Increases in either total Aβ levels or the relative concentration of both Aβ40 and Aβ42 (where the former is more concentrated in cerebrovascular plaques and the latter in neuritic plaques) have been implicated in the pathogenesis of both familial and sporadic Alzheimer's disease. (wikipedia.org)
The "amyloid hypothesis" - that the plaques are responsible for the pathology of Alzheimer's disease - is accepted by the majority of researchers, but is not conclusively established. (wikipedia.org)
The search to find therapeutic targets in Alzheimer's disease (AD) has been dominated for over 25 years by research into the roles in the initiation and progression of dementia of the amyloid beta protein (Aβ) [1, 2], derived from the β-pathway of amyloid beta protein (AβPP) cleavage. (j-alz.com)
Mutations in the presenilin 1 gene, PSEN1, which cause familial Alzheimer's disease alter the processing of amyloid precursor protein, leading to the generation of various amyloid-ß peptide species. (bvsalud.org)
Investigating differences in underlying molecular mechanisms of familial Alzheimer's disease may inform our understanding of clinical heterogeneity. (bvsalud.org)
Secretase processing of mutant BRI2 leads to secretion and deposition of BRI2-derived amyloidogenic peptides, ABri and ADan that resemble APP/ß-amyloid (Aß) pathology, which is characteristic of Alzheimer's disease (AD). (bvsalud.org)
Micrograph of a section of the cerebral cortex from a person with Alzheimer's disease , immunostained with an antibody to amyloid beta (brown), a protein fragment that accumulates in amyloid plaques and cerebral amyloid angiopathy . (wikipedia.org)
[9] However, some proteinaceous lesions lack birefringence and contain few or no classical amyloid fibrils, such as the diffuse deposits of amyloid beta (Aβ) protein in the brains of people with Alzheimer's. (wikipedia.org)
they provide insight into the factors that drive amyloid plaque development and are potential biomarkers or therapeutic targets for Alzheimer's disease (AD). (researchsquare.com)
Amyloid plaques are a neuropathological hallmark of Alzheimer's disease and primarily consist of the protein beta amyloid (Aβ). (researchsquare.com)
[6] APP is best known as the precursor molecule whose proteolysis generates amyloid beta (Aβ), a polypeptide containing 37 to 49 amino acid residues, whose amyloid fibrillar form is the primary component of amyloid plaques found in the brains of Alzheimer's disease patients. (handwiki.org)
Mutations in critical regions of amyloid precursor protein, including the region that generates amyloid beta (Aβ), cause familial susceptibility to Alzheimer's disease. (handwiki.org)
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the most cases of dementia, which is characterized by the deposition of dense plaques of amyloid beta (Aβ) plaques and neurofibrillary tangles consisting of hyperphosphorylated tau. (oncotarget.com)
Protein19
The peptides derive from the amyloid-beta precursor protein (APP), which is cleaved by beta secretase and gamma secretase to yield Aβ in a cholesterol-dependent process and substrate presentation. (wikipedia.org)
The plaques are composed of a tangle of Aβ oligomers and regularly ordered aggregates called amyloid fibrils, a protein fold shared by other peptides such as the prions associated with protein misfolding disease, also known as Proteinopathy. (wikipedia.org)
Significant efforts have been focused on the mechanisms responsible for Aβ production, including the proteolytic enzymes gamma- and β-secretases which generate Aβ from its precursor protein, APP (amyloid precursor protein). (wikipedia.org)
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)
We assessed both the amyloid-ß peptide profiles and presenilin 1 protein maturity. (bvsalud.org)
Familial British dementia (FBD) and familial Danish dementia (FDD) are autosomal dominant forms of dementia caused by mutations in the integral membrane protein 2B (ITM2B, also known as BRI2) gene. (bvsalud.org)
Amyloid fibrils are protein polymers comprising identical monomer units (homopolymers). (medscape.com)
All recognized mutations for AD are associated with increased deposition of amyloid-beta (Abeta), a peptide fragment comprising 39-43 amino acids that derive from the catabolism of the amyloid precursor protein (APP) molecule. (medscape.com)
The amino acid changes could alter the protein charge and stability, inducing distinct physiological functions. (dovepress.com)
proteinopathic adj ), or proteopathy , protein conformational disorder , or protein misfolding disease , is a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells , tissues and organs of the body. (wikipedia.org)
In 1859, Friedreich and Kekulé demonstrated that, rather than consisting of cellulose, "amyloid" actually is rich in protein. (wikipedia.org)
The neuropathologic hallmarks of AD are senile plaques composed of extracellular deposits of amyloid-β (Aβ) and neurofibrillary tangles composed of intracellular aggregates of tau protein with multiple post-translational modifications including phosphorylation. (biomedcentral.com)
TDP-43 is a 43 kDa heterogeneous nuclear ribonuclear protein (hnRNP) composed of 414 amino acids and is encoded by the TARDBP gene located on chromosome 1 (1p36.22) [ 14 ]. (biomedcentral.com)
Amyloid-beta precursor protein ( APP ) is an integral membrane protein expressed in many tissues and concentrated in the synapses of neurons . (handwiki.org)
Amyloid-beta precursor protein is an ancient and highly conserved protein . (handwiki.org)
[12] The amyloid beta region of the protein, located in the membrane-spanning domain, is not well conserved across species and has no obvious connection with APP's native-state biological functions. (handwiki.org)
The key pathological changes observed in AD brain tissue are amyloid beta (Aβ) peptide deposited and neuritic plaques, hyperphosphorylated tau protein and neurofibrillary tangles [ 4 , 5 ]. (oncotarget.com)
Pathology4
This approach has never been fully accepted by the AD research community [6-12] and epidemiological population based studies of ageing consistently find complex relationships between age, amyloid pathology, in-life factors such as education, and dementia status [13-17]. (j-alz.com)
Amyloid pathology in FBD/FDD manifests itself predominantly in the microvasculature by ABri/ADan containing cerebral amyloid angiopathy (CAA). (bvsalud.org)
This adds preliminary human data to an emerging body of animal data suggesting that tau pathogenesis occurs downstream of amyloid pathology and that amyloid removal can hold its early stages at bay. (alzforum.org)
We focused our study on early onset AD as the drivers of the more aggressive pathology development in these cases is unknown and it is unclear whether amyloid-plaque enriched proteins differ between subtypes of early onset AD. (researchsquare.com)
Fibrils5
Amyloidosis is a clinical disorder caused by extracellular and/or intracellular deposition of insoluble abnormal amyloid fibrils that alter the normal function of tissues. (medscape.com)
Only 10% of amyloidosis deposits consist of components such as glycosaminoglycans (GAGs), apolipoprotein-E (apoE), and serum amyloid P-component (SAP), while nearly 90% of the deposits consist of amyloid fibrils that are formed by the aggregation of misfolded proteins. (medscape.com)
[ 4 ] In humans, about 23 different unrelated proteins are known to form amyloid fibrils in vivo. (medscape.com)
The modern era of amyloidosis classification began in the late 1960s with the development of methods to solubilize amyloid fibrils. (medscape.com)
320) Eto M, Hashimoto T, Shimizu T, Iwatsubo T: Characterization of the unique in vitro effects of unsaturated fatty acids on the formation of amyloid beta fibrils. (u-tokyo.ac.jp)
Deposition1
While ABri and ADan peptide sequences differ only in a few C-terminal amino acids, CAA in FDD is characterized by co-aggregation of ADan with Aß, while in contrast no Aß deposition is observed in FBD. (bvsalud.org)
Peptide5
Mutation-specific amyloid-ß peptide profiles may thereby influence pathogenicity and clinical heterogeneity. (bvsalud.org)
We also compared amyloid-ß peptide profiles in human post-mortem brain tissue from cases with matched mutations. (bvsalud.org)
Distinct amyloid-ß peptide patterns were also observed in human brain tissue from individuals with these mutations, showing some similar patterns to cell line observations. (bvsalud.org)
Functional amyloids play a beneficial role in a variety of physiologic processes (eg, long-term memory formation, gradual release of stored peptide hormones). (medscape.com)
APOE binds to cell-surface receptors to deliver lipids and to the hydrophobic amyloid-β peptide, regulating amyloid-β aggregations and clearances in the brain. (dovepress.com)
Aggregation2
Taking the immunoreactivity profiles of the anti-Aβ antibodies 6E10 and 6F3D seen in human brain tissues [21], beyond considerations of aggregation state, is the lower reactivity of 6E10 also associated with N-terminal truncations or other modifications [23]? (j-alz.com)
The familial aggregation of AD shows that genetic factors may play a vital essential role in the development of the disease [ 6 - 8 ]. (oncotarget.com)
Aβ deposits within the walls of blood vessels in the form of amyloid angiopathy are found in many patients with AD, but it is also found in other neurologic disorders [ 2 ]. (biomedcentral.com)
Amyloidosis3
Carriers of this mutation develop a severe hereditary form of cerebral amyloid angiopathy (CAA), known as hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D). This disease is associated with recurrent strokes during the fifth and sixth decades of life often causing focal neurological symptoms and signs, including focal seizures. (alzforum.org)
Some classification systems included myeloma-associated, familial, and localized amyloidosis. (medscape.com)
Amyloidosis results from the accumulation of pathogenic amyloids-most of which are aggregates of misfolded proteins-in a variety of tissues. (medscape.com)
Fibrillar1
[9] Subsequent research has shown that many different proteins can form amyloid, and that all amyloids show birefringence in cross- polarized light after staining with the dye Congo red , as well as a fibrillar ultrastructure when viewed with an electron microscope . (wikipedia.org)
The aim of this study was to comprehensively identify proteins that are enriched in amyloid plaques using unbiased proteomics in two subtypes of early onset AD: sporadic early onset AD (EOAD) and Down Syndrome (DS) with AD. (researchsquare.com)
Amyloid plaques and neighbouring non-plaque tissue were microdissected from human brain sections using laser capture microdissection and label-free LC-MS was used to quantify the proteins present. (researchsquare.com)
Many of these proteins were more significantly enriched in amyloid plaques than Aβ. (researchsquare.com)
The most enriched proteins in amyloid plaques in both EOAD and DS were: COL25A1, SMOC1, MDK, NTN1, OLFML3 and HTRA1. (researchsquare.com)
Endosomal/lysosomal proteins were particularly highly enriched in amyloid plaques. (researchsquare.com)
Fluorescent immunohistochemistry was used to validate the enrichment of four proteins in amyloid plaques (moesin, ezrin, ARL8B and SMOC1) and to compare the amount of total Aβ, Aβ40, Aβ42, phosphorylated Aβ, pyroglutamate Aβ species and oligomeric species in EOAD and DS. (researchsquare.com)
Overall, we observed that amyloid plaques in EOAD and DS largely contained the same proteins, however the amount of enrichment of some proteins was different in EOAD and DS. (researchsquare.com)
Our study highlights the significant enrichment of many proteins in amyloid plaques, many of which may be potential therapeutic targets and/or biomarkers for AD. (researchsquare.com)
However, it is often overlooked that amyloid plaques also contain hundreds of proteins in addition to Aβ. (researchsquare.com)
Therefore, comprehensively profiling the proteins that are enriched in amyloid plaques would increase our understanding about AD pathogenesis, and possibly identify new biomarkers and/or new therapeutic targets for AD. (researchsquare.com)
Mass spectrometry-based proteomics is an alternative approach that allows efficient quantification of thousands of amyloid plaque proteins simultaneously. (researchsquare.com)
Deposits3
Evidence suggests that while P3-40 is seen in the soluble compartment, P3-42 is not [19], though it has been detected neuropathologically in fleecy amyloid deposits [22]. (j-alz.com)
Various descriptive classification systems were proposed based on the organ distribution of amyloid deposits and clinical findings. (medscape.com)
Senile plaques are complicated and heterogeneous lesions that contain not only amyloid deposits and tau positive neurites, but also neurites with degenerating pre- and post-synaptic elements (so-called dystrophic neurites), as well as activated microglia and reactive astrocytes [ 1 ]. (biomedcentral.com)
Sporadic2
The commonest form, sporadic amyloid-ß CAA, usually affects people in mid- to later life. (bvsalud.org)
mutations of PSEN1 and PSEN2) and non-amyloid-ß CAA (associated with ITM2B, CST3, GSN, PRNP and TTR mutations), and other unusual sporadic and acquired causes including the newly-recognized iatrogenic subtype. (bvsalud.org)
Mutations1
Extracellular vesicle DNA from human melanoma tissues contains cancer-specific mutations. (gu.se)
Plaques contain1
Amyloid plaques contain both Aβ40 and Aβ42, while vascular amyloid is predominantly the shorter Aβ40. (wikipedia.org)
Accumulates1
Extensive Aβ accumulates in the cerebral vessels, especially the meningeal arteries and the cerebro-cortical arterioles. (alzforum.org)
Cortex1
Micrograph of immunostained α-synuclein (brown) in Lewy bodies (large clumps) and Lewy neurites (thread-like structures) in the cerebral cortex of a patient with Lewy body disease , a synucleinopathy . (wikipedia.org)
Beta3
The glymphatic system clears metabolic waste from the mammalian brain, and in particular amyloid beta. (wikipedia.org)
[ 1 ] 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)
This substitution is adjacent to the beta secretase cleavage site and results in a 40% reduction in the formation of amyloid beta in vitro. (handwiki.org)
ApoE2
The apolipoprotein E (APOE) gene is located on chromosome 19 and encodes a glycoprotein that is 299 amino acids long. (dovepress.com)
APOE is a 299 amino acid plasma glycoprotein associated with LDL, VLDL, and high-density lipoproteins (HDL). (dovepress.com)
Interstitial1
Amorphous eosinophilic interstitial amyloid observed on a renal biopsy. (medscape.com)
Hypothesis2
An alternative hypothesis is that amyloid oligomers rather than plaques are responsible for the disease. (wikipedia.org)
different groups have proposed different routes including microglia devouring amyloid and the peripheral sink hypothesis. (alzforum.org)
Clinical1
The recent failures of clinical trials demand that we re-examine the amyloid approach in detail. (j-alz.com)
Vessel2
This mutation results in the accumulation of Aβ in cerebral vessel walls which is associated with cell death and loss of vessel wall integrity. (alzforum.org)
Cerebral amyloid angiopathy (CAA) is an important cerebral small vessel disease associated with brain haemorrhage and cognitive change. (bvsalud.org)
Form2
However the central sequence KLVFFAE is known to form amyloid on its own, and probably forms the core of the fibril. (wikipedia.org)
Phospholipases A 2 (PLA 2 ) form a superfamily of enzymes that catalyze production of lyso-phospholipids and free fatty acids by the hydrolysis of phospholipids sn-2 ester bond. (pharmaceuticalintelligence.com)
Substance2
Until the early 1970s, the idea of a single amyloid substance predominated. (medscape.com)
The concept of proteopathy can trace its origins to the mid-19th century, when, in 1854, Rudolf Virchow coined the term amyloid ("starch-like") to describe a substance in cerebral corpora amylacea that exhibited a chemical reaction resembling that of cellulose . (wikipedia.org)
Fragments1
The current practice of interpreting immunoreactivities seen with commonly used antibodies as "Aβ" without controlling for the other fragments misleads the entire amyloid based research approach. (j-alz.com)
Heterogeneity1
The first difficulty is the heterogeneity of what we understand as the Aβ amino acid sequence. (j-alz.com)
Significantly1
Amyloid-ß ratios significantly differed compared with controls and between different patients, implicating mutation-specific alterations in amyloid-ß ratios. (bvsalud.org)
Pathways1
The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
Brain1
1 It is synthesized in various tissues in the body including the liver, brain, and skin and in macrophages. (dovepress.com)
Liver1
Micrograph of amyloid in a section of liver that has been stained with the dye Congo red and viewed with crossed polarizing filters, yielding a typical orange-greenish birefringence. (wikipedia.org)
Subsequent1
Therefore, we propose that damage to and subsequent release of mtDNA elicits a protective signalling response that enhances nDNA repair in cells and tissues, suggesting that mtDNA is a genotoxic stress sentinel. (regenerativemedicine.net)
Cells2
The amyloid-ß43:40 ratio was increased in R278I and both E280G lines compared with controls, but not in M146I cells. (bvsalud.org)
Mammalian sperm cells present highly specific lipidic composition, high content of polyunsaturated fatty acids, plasmalogenes and sphingomyelins. (scialert.net)
Component1
331) Hashimoto T, Fujii D, Naka Y, Kashiwagi-Hakozaki M, Matsuo Y, Matsuura Y, Wakabayashi T, Iwatsubo T: Collagenous Alzheimer amyloid plaque component impacts on the compaction of amyloid-β plaques. (u-tokyo.ac.jp)