Brain parenchymal and microvascular amyloid in Alzheimer's disease.
Brains of patients with Alzheimer disease/senile dementia of Alzheimer type (AD/SDAT) develop a progressive accumulation of amyloid, which deposits primarily in the form of characteristic parenchymal 'plaques' (senile or neuritic plaques/SP's) and as mural deposits in the walls of capillaries and arterioles (cerebral amyloid angiopathy /CAA). A major component of this amyloid is a small and unique peptide composed of 39-43 amino acids, beta/A4, which is cleaved from a much larger precursor protein (APP) that has several isoforms. Brain amyloid can be detected in autopsy or biopsy brain tissue by classical, immunohistochemical and ultrastructural (including immuno-electron microscopic) methods of varying sensitivity and specificity. Beta/A4 amyloid deposition is remarkably variable (e.g. predominantly parenchymal or vascular, or a mixture of parenchymal and vascular) among patients with AD/SDAT. Despite its abundance in the brains of AD/SDAT patients, the precise role of beta/A4 in the pathogenesis of the neurological deficit, neocortical atrophy and progressive synapse loss associated with AD/SDAT has yet to be determined. However, mutations in the gene that encodes APP are clearly associated with familial AD syndromes in which there is significant brain amyloid deposition. CAA, in addition to its association with AD/SDAT, can result in hemorrhagic and (possibly) ischemic forms of stroke. Work with recently developed transgenic mice which express large amounts of beta/A4 in the central nervous system is likely to elucidate mechanisms by which the protein is selectively or deposited in the brain in a parenchymal or microvascular form, and how it contributes to the pathogenesis of neurodegeneration.
Vinters
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HV
Department of Pathology & Laboratory Medicine, UCLA Medical Center 90095-1732, USA.
Wang
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Secor
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DL
D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D000682:Amyloid / Q000032:analysis*; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000818:Animals; D001160:Arterioles / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D002196:Capillaries / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology; D002560:Cerebrovascular Circulation; D006801:Humans; D008578:Meninges / Q000098:blood supply / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008833:Microcirculation / Q000473:pathology*
D000682:Amyloid; D016229:Amyloid beta-Peptides