• 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)
  • Amyloid fibrils are protein polymers comprising identical monomer units (homopolymers). (medscape.com)
  • Amyloidosis is a clinical disorder caused by extracellular and/or intracellular deposition of insoluble abnormal amyloid fibrils that alter the normal function of tissues. (medscape.com)
  • [ 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)
  • 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)
  • [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)
  • 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)
  • 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)
  • 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)
  • Protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells, thereby templating their own aberrant conformation onto soluble homotypic proteins. (bvsalud.org)
  • RepA is a bacterial protein that builds intracellular amyloid oligomers acting as inhibitory complexes of plasmid DNA replication. (bvsalud.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)
  • The amino acid changes could alter the protein charge and stability, inducing distinct physiological functions. (dovepress.com)
  • 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)
  • In 1859, Friedreich and Kekulé demonstrated that, rather than consisting of cellulose, "amyloid" actually is rich in protein. (wikipedia.org)
  • [10] Furthermore, evidence has emerged that small, non-fibrillar protein aggregates known as oligomers are toxic to the cells of an affected organ, and that amyloidogenic proteins in their fibrillar form may be relatively benign. (wikipedia.org)
  • [5] In this aggregated form, the protein is resistant to clearance and can interfere with the normal capacity of the affected organs. (wikipedia.org)
  • For example, cystic fibrosis is caused by a defective cystic fibrosis transmembrane conductance regulator (CFTR) protein, [3] and in amyotrophic lateral sclerosis / frontotemporal lobar degeneration (FTLD), certain gene-regulating proteins inappropriately aggregate in the cytoplasm, and thus are unable to perform their normal tasks within the nucleus. (wikipedia.org)
  • Amyloid plaques are a neuropathological hallmark of Alzheimer's disease and primarily consist of the protein beta amyloid (Aβ). (researchsquare.com)
  • 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)
  • Amyloidosis results from the accumulation of pathogenic amyloids-most of which are aggregates of misfolded proteins-in a variety of tissues. (medscape.com)
  • Using different cellular models propagating prions or pathogenic Tau aggregates, we demonstrate that vesicular stomatitis virus glycoprotein and SARS-CoV-2 spike S increase aggregate induction by cell contact or ligand-decorated EV. (bvsalud.org)
  • Aβ molecules can aggregate to form flexible soluble oligomers which may exist in several forms. (wikipedia.org)
  • An alternative hypothesis is that amyloid oligomers rather than plaques are responsible for the disease. (wikipedia.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • Aβ can also form the deposits that line cerebral blood vessels in cerebral amyloid angiopathy. (wikipedia.org)
  • Various descriptive classification systems were proposed based on the organ distribution of amyloid deposits and clinical findings. (medscape.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)
  • 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)
  • [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)
  • Amyloid plaques contain many proteins in addition to beta amyloid (Aβ). (researchsquare.com)
  • 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)
  • 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)
  • 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)
  • 48 proteins were consistently enriched in amyloid plaques in EOAD and DS. (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)
  • Previous studies have typically used immunohistochemistry to identify amyloid plaque proteins. (researchsquare.com)
  • Mass spectrometry-based proteomics is an alternative approach that allows efficient quantification of thousands of amyloid plaque proteins simultaneously. (researchsquare.com)
  • 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)
  • 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)
  • Amyloid plaques contain both Aβ40 and Aβ42, while vascular amyloid is predominantly the shorter Aβ40. (wikipedia.org)
  • Extensive Aβ accumulates in the cerebral vessels, especially the meningeal arteries and the cerebro-cortical arterioles. (alzforum.org)
  • 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)
  • 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)
  • 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)
  • These aggregates may consist of oligomeric complexes of non-native secondary structures and demonstrate poor solubility in aqueous or detergent solvents [ 3 ]. (biomedcentral.com)
  • The glymphatic system clears metabolic waste from the mammalian brain, and in particular amyloid beta. (wikipedia.org)
  • [ 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • The recent failures of clinical trials demand that we re-examine the amyloid approach in detail. (j-alz.com)
  • The first difficulty is the heterogeneity of what we understand as the Aβ amino acid sequence. (j-alz.com)
  • 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)
  • Congo red staining of a cardiac biopsy specimen containing amyloid, viewed under polarized light. (medscape.com)
  • Six phenotypes were observed as a result of two single nucleotide polymorphisms (SNPs) at amino acid positions 112 and 158. (dovepress.com)
  • A study has suggested that APP and its amyloid potential is of ancient origins, dating as far back as early deuterostomes. (wikipedia.org)
  • In addition to severe hemorrhages, extensive amyloid develops in the vasculature. (alzforum.org)