Beta-amyloid fibrils of Alzheimer's disease: pathologically altered, basement membrane-associated microfibrils?
Beta amyloid fibrils were examined in situ in the cerebral cortex of brains from patients with Alzheimer's disease using high resolution ultrastructural and immunohistochemical techniques. The main body of the fibril was identical with that of microfibrils and was made up of a core containing amyloid P component (AP), and a surface layer. Beta amyloid protein (Abeta) in the form of 1 nm wide flexible filaments was associated with the external surface of the microfibril. In cerebrovascular amyloid angiopathy the fibrils were formed at the outer surface of the vascular basement membrane. Overproduction of microfibrils has been reported at the basement membrane of "leaky" capillaries including the glomerular capillary in disease or leaky alveolar-capillary walls of normal lungs. Similarly, in Alzheimer's disease overproduction of microfibril-like beta amyloid fibrils in amyloid angiopathy coincided with breakdown of the blood-brain barrier of the cerebromicrovasculature. Thus, in the above three locations, the presence of abundant microfibrils, or microfibril-like structures, may be related to plasma which leaks out of the circulation into the adjoining vascular basement membrane. AP is an essential constituent of microfibrils and since the only site where AP is available in the cerebral cortex is in leaky microvasculature, a chronic, steady supply of AP into perivascular areas may be the cause of overproduction of microfibrils. Brain "microfibrils" may further be altered pathologically into beta amyloid fibrils by the addition of Abeta. The origin of the fibrils in senile plaques may also be the microvasculature since in the area of the plaques no source of AP is apparent.
Inoue
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S
Department of Anatomy and Cell Biology, McGill Univeristy, Montreal, Quebec, Canada. mdin@musica.mcgill.ca
Kisilevsky
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R
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000648:ultrastructure*; D001485:Basement Membrane / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D002196:Capillaries / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D002199:Capillary Permeability / Q000502:physiology; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D020894:Microfibrils / Q000473:pathology* / Q000648:ultrastructure; D008854:Microscopy, Electron; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure
D016229:Amyloid beta-Peptides