Basement membranes, microfibrils and beta amyloid fibrillogenesis in Alzheimer's disease: high resolution ultrastructural findings.

It is known that beta amyloid fibrils are deposited at the basement membrane of the cerebromicrovasculature in the brains of patients with Alzheimer's disease, and the assembly of the fibrils may be in continuation with the core of senile plaques. The fibrils accumulate in a manner similar to that in which microfibrils accumulate in the glomerular basement membrane of the rat kidney during long-term experimental diabetes, and in the alveolar-capillary basement membrane of the normal lung. beta amyloid fibrils in-situ are known to be about 10 nm wide tubular structures and they closely resemble connective tissue microfibrils. Our recent high resolution ultrastructural studies combined with immunogold labeling demonstrated that beta amyloid fibrils in-situ are indeed microfibril-like structures, and the beta protein is associated with their surface in the form of loose assemblies of 1 nm wide flexible filaments. Thus, the result of this study indicates that in-situ a major component of the beta amyloid deposit is the microfibril-like structure. The elucidation of the mechanism of cerebral beta amyloid fibrillogenesis in Alzheimer's disease may therefore require understanding the mechanism of 'normal' microfibrils biogenesis.
(Copyright 1999 Elsevier Science B.V.)