Basement membrane and beta amyloid fibrillogenesis in Alzheimer's disease.
High-resolution ultrastructural and immunohistochemical studies revealed that in situ beta amyloid fibrils of Alzheimer's disease were made up of a core consisting of a solid column of amyloid P component (AP) and associated chondroitin sulfate proteoglycan, and a heparan sulfate proteoglycan surface layer with externally associated fine filaments of beta protein. The main body of beta amyloid fibrils closely resembled that of microfibrils. Abundant microfibrils were reported to be present at the basement membrane of capillaries with "leaky" blood-urine or blood-air barriers. Similarly, abundant microfibril-like beta amyloid fibrils are formed at the microvascular basement membrane in cerebrovascular amyloid angiopathy with altered blood-brain barrier. Since AP is an indispensable major component of microfibrils and microfibril-like structures, the formation of microfibrils may depend on, among other factors, the availability of AP. Thus, in beta amyloid fibrillogenesis fibrils may be built around AP which continuously leaks out from circulation into vascular basement membrane, and beta amyloid fibrils may be regarded as pathologically altered basement membrane-associated microfibrils. With no source of AP around them, senile plaque fibrils may also be derived from perivascular amyloid.
Inoue
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Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001485:Basement Membrane / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D001921:Brain / Q000473:pathology; D002199:Capillary Permeability; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020894:Microfibrils / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D011487:Protein Conformation; D021122:Protein Subunits; D000683:Serum Amyloid P-Component / Q000737:chemistry* / Q000378:metabolism
D016229:Amyloid beta-Peptides; D011508:Chondroitin Sulfate Proteoglycans; D019812:Heparan Sulfate Proteoglycans; D021122:Protein Subunits; D000683:Serum Amyloid P-Component