Soluble Alzheimers beta-amyloid constricts the cerebral vasculature in vivo

Bilateral temporoparietal hypoperfusion has been frequently observed early in the Alzheimer's disease (AD) process. An increased beta-amyloid (A beta) peptide is believed to play a central role in the pathogenesis of AD. In v itro experiments have shown that freshly solubilized A beta enhances constr iction of cerebral and peripheral vessels. We propose that in vivo the A be ta vasoactive property may contribute to cerebral hypoperfusion of AD patie nts. To test this hypothesis, we intra-arterially infused freshly solubiliz ed A beta 1-40 in rats and observed changes in cerebral blood flow and cere brovascular resistance using fluorescent microspheres. We found that infusi on of A beta in vivo resulted in a decreased blood flow and increased vascu lar resistance specifically in cerebral cortex but not in heart or kidneys. These data suggest that A beta has a direct and specific constrictive effe ct on cerebral vessels in vivo, which may contribute to the cerebral hypope rfusion observed early in the AD process. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.