Microangiopathy, the vascular basement membrane and Alzheimer's disease: a review.

The present review focuses on the vascular basement membrane (VBM) and its relationship to the lesions of Alzheimer's disease (AD). Examination of the fine structure of the microvasculature reveals AD-associated VBM alterations, which include both thickening and vacuolization. Immunocytochemistry confirms that all three intrinsic VBM components [collagen type IV, laminin, and heparan sulfate proteoglycan (HSPG)] outline the capillary bed, which is pathologically altered in AD patients (microangiopathy). Ultrastructural analyses of AD tissue samples demonstrate that HSPG's normal staining pattern is disrupted on the endothelial surface of the VBM in brain regions affected by Alzheimer lesions. Similarly altered VBM is reported to occur in the kidney of patients with diabetes mellitus, where it is associated with a leakage of protein. All three VBM components immunolabel capillaries, amyloid and plaque-associated glial processes, suggesting a link between microangiopathy and senile plaque formation. In addition, the consistent colocalization of HSPG with several forms of amyloid implies an involvement in amyloidogenesis. Finally, the neurotrophic effects of beta-amyloid, combined with neurite-promoting effects of laminin and HSPG, could create a strong focus for an aberrant sprouting response. Such a response is postulated to result in plaque-associated degenerating neurites. Thus, VBM components could serve as a nidus for plaque formation, playing a role in the development of neuritic as well as amyloidotic elements.