Disease relevance of Senile Plaques

• Localization of the corresponding genomic sequences on human chromosome 21 suggests a genetic relationship between Alzheimer disease and Down syndrome, and it may explain the early appearance of large numbers of neuritic plaques in adult Down syndrome patients [1].
• The levels of insoluble Abeta in the leptomeninges or cortex generally correlated with the degree of cerebral amyloid angiopathy or the abundance of senile plaque, respectively [2].
• The index case with the presenilin-2 mutation had late-onset dementia at age 73 years, died of an acute intracerebral hemorrhage, and pathologically showed severe amyloid angiopathy but only rare neuritic senile plaques and neurofibrillary tangles [3].
• Neuropathological examination in that patient showed meningoencephalitis, and focal atypically low numbers of diffuse and neuritic plaques but not of vascular amyloid, nor regression of tau pathology in neurofibrillary tangles and neuropil threads [4].
• Common features of the phenotype of 14qFAD in the L family included onset of dementia before the age of 50, early progressive aphasia, early-appearing myoclonus and generalized seizures, paratonia, cortical atrophy, numerous and extensive senile plaques and neurofibrillary tangles, and prominent amyloid angiopathy [5].

Psychiatry related information on Senile Plaques

• Absence of aluminium in neuritic plaque cores in Alzheimer's disease [6].
• Clinical dementia, neuritic plaques, and old age per se are not correlated with increased ADAP levels [7].
• Anti-beta-peptide stained cerebrovascular and plaque core amyloid in all AD cases as well as cerebrovascular amyloid and senile plaque core amyloid in five elderly CJD cases [8].

High impact information on Senile Plaques

• These mutations in PrP are the first to be associated with the appearance of both PrP amyloid plaques and neocortical NFTs in GSS patients [9].
• The amyloid beta-protein precursor gives rise to the amyloid beta-protein, the principal constituent of senile plaques and a cytotoxic fragment involved in the pathogenesis of Alzheimer disease [10].
• Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease [11].
• A constituent of senile plaques in AD is beta-amyloid, a hydrophobic peptide of 39-43 amino acids and a fragment of the amyloid precursor protein (APP) [12].
• However, although the main protein components of NFT and senile plaques, tau (tau) and amyloid beta-protein, respectively, are well characterized, the molecular mechanisms responsible for their deposition in lesions are unknown [13].

Chemical compound and disease context of Senile Plaques

• In Alzheimer's disease, synuclein/NAC (non-amyloid beta component of Alzheimer's disease amyloid) proteins are found in presynaptic cholinergic nerve terminals that degenerate early in Alzheimer's disease, and they are also found closely linked to beta-amyloid fibrils in senile plaques [14].
• The beta-amyloid peptide is a major component of the cerebral amyloid plaque in Alzheimer disease and has been shown to be neurotoxic [15].
• Collagen XVIII: a novel heparan sulfate proteoglycan associated with vascular amyloid depositions and senile plaques in Alzheimer's disease brains [16].
• The present paper examines the relationship between choline acetyltransferase (ChAT) activity and gamma aminobutyric acid (GABA) concentrations with neuronal counts, senile plaque counts and estimates of neurofibrillary tangles in a series of 25 cases of senile dementia of Alzheimer type (SDAT) with appropriate controls [17].
• In areas of moderately impaired local cerebral metabolic rate of glucose, as revealed by reduced FDG uptake, there was some gliosis, primarily around the numerous senile plaques [18].

Biological context of Senile Plaques

• No analogous relationship was found between the phosphorylation of B50/GAP-43 and the density of neuritic plaques in the brains examined [19].
• Microglial cells and astrocytes are closely associated with nearly all compact deposits of the amyloid beta-protein found in the senile plaques characteristic of Alzheimer's disease and trisomy 21 [20].
• This approach involves the deliberate induction of an autoimmune response to amyloid-beta (Abeta) peptide, the constituent of neuritic plaques that is thought to cause the neurodegeneration and dementia in AD [21].
• The amyloidogenic pathway leading to the production and deposition of Abeta peptides, major constituents of Alzheimer disease senile plaques, is linked to neuronal metal homeostasis [22].
• The rationale is particularly strong for targeting the deposition of amyloid into neuritic plaques, but attention has also turned to abnormalities in apoptosis and signal-transduction processes [23].

Anatomical context of Senile Plaques

• The appearance of these amyloid-associated abnormal cholinergic processes was similar to that of neurites in senile plaques, as shown by conventional silver impregnation techniques [24].
• Choline acetyltransferase levels were significantly correlated with severity of neuropathological lesions of AD, as measured by density of neuritic plaques and neurofibrillary tangles [25].
• Progressive amyloid deposition in senile plaques and cortical blood vessels may play a central role in the pathogenesis of Alzheimer disease [26].
• Distribution of precursor amyloid-beta-protein messenger RNA in human cerebral cortex: relationship to neurofibrillary tangles and neuritic plaques [27].
• In situ enzyme histochemistry of cathepsin D and cathepsin B on sections of neocortex using synthetic peptides and protein substrates showed that senile plaques contained the highest levels of enzymatically active cathepsin [28].

Associations of Senile Plaques with chemical compounds

• The stability of proteins that constitute the neurofibrillary tangles and senile plaques of Alzheimer disease suggests that they would be ideal substrates for nonenzymatic glycation, a process that occurs over long times, even at normal levels of glucose, ultimately resulting in the formation of advanced glycation end products (AGEs) [29].
• There was a positive correlation (r = 0.914) between kainate binding and senile plaque number in deep cortical layers [30].
• The resulting 39-43 amino acid beta-amyloid may be neurotoxic and disrupt neuronal connectivity after its accumulation in senile plaques [31].
• We conclude that collagen XVIII is a novel heparan sulfate proteoglycan associated with vascular A beta and classic senile plaques and that at least the long form of collagen XVIII accumulates in amyloid-laden vessels and classic senile plaques [16].
• Of the 20 samples from Nairobi, 3 (15%) brains exhibited neocortical A beta deposits that varied from numerous diffuse to highly localized compact or neuritic plaques, many of which were also thioflavin S positive [32].

Gene context of Senile Plaques

• The regulation of extracellular proteolysis by PN-II and the deposition of at least parts of the molecule in senile plaques is consistent with previous reports that implicate altered proteolysis in the pathogenesis of Alzheimer's disease [33].
• ApoE-epsilon 4/4 patients had more senile plaques (SPs) than epsilon 3/3 patients [34].
• Isoform-specific differences have been identified in the binding of apoE to the microtubule-associated protein tau, which forms the paired helical filament and neurofibrillary tangles, and to amyloid beta peptide, a major component of the neuritic plaque [35].
• Amyloid precursor protein (APP) is endoproteolytically processed by BACE1 and gamma-secretase to release amyloid peptides (Abeta40 and 42) that aggregate to form senile plaques in the brains of patients with Alzheimer's disease (AD) [36].
• alpha2-Macroglobulin (A2M) is a proteinase inhibitor found in association with senile plaques (SP) in Alzheimer's disease (AD) [37].

Analytical, diagnostic and therapeutic context of Senile Plaques

• Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides [1].
• Immunoelectron microscopy of diffuse and mature neuritic plaques shows that PKC(beta II)-like immunoreactivity in the plaques is closely associated with membranous structures of fine neuronal processes apposed to the amyloid fibers [38].
• By double label immunohistochemistry, some pyramidal neurons coexpressed superoxide dismutases and tau, and a few copper, zinc-superoxide dismutase-positive structures in senile plaques colocalized with tau [39].
• Here, we investigated the effects of lovastatin on beta-amyloid production and senile plaque deposition in an animal model of AD (Tg2576 mice) [40].
• Western blot analysis revealed no alterations in the level of synaptic, neuronal, or glial markers in neocortex or hippocampus and histologic analysis revealed no evidence of Abeta deposition or neuritic plaques in the apoE KO/TG mice [41].

References