VASCULAR BASEMENT-MEMBRANE COMPONENTS AND THE LESIONS OF ALZHEIMERS-DISEASE - LIGHT AND ELECTRON-MICROSCOPIC ANALYSES

Alzheimer's disease (AD) is one of several systemic and cerebral disea ses that involve the abnormal deposition of fibrillar proteins called amyloids. All amyloids share conformational and staining characteristi cs, as well as an association with resident tissue macrophages and two extracellular matrix components [heparan sulfate proteoglycan (HSPG) and amyloid P component]. Vascular, glomerular, and Schwann cell basem ent membrane pathologies have been documented in many forms of amyloid osis, and often amyloid fibrils fuse to and project from the basement membrane in these diseases. The present report demonstrates the vascul ar basement membrane (VBM) alterations in AD autopsy samples, and deta ils the methodologies used. Electron microscopy reveals the fusion of amyloid fibrils with the VBM and the alteration of the VBM in the abse nce of amyloid accumulation. Double-labelling and pre-embed immuno-ele ctron microscopy techniques demonstrate the colocalization of amyloid P component and VBM components with amyloid, and also reveal that amyl oid P component is not localized to the cerebral VBM. Finally, a novel correlative light/electron microscopy technique demonstrates the asso ciation between amyloid P component and cerebral resident tissue macro phages, the microglia. Taken together, these data suggest that the phy sicochemical processes of amyloid formation, rather than amyloid depos ition, may be responsible for VBM pathology. (C) 1994 Wiley-Liss, Inc.