A beta vasoactivity in vivo

Bilateral temporoparietal hypoperfusion has been frequently observed early in the Alzheimer's disease (AD) process. The beta-amyloid (A beta) peptide is believed to play a central role in the pathogenesis of AD. In vitro experiments have shown that freshly solubilized A beta enhances constriction of cerebral and peripheral vessels. We proposed that in vivo, A beta would also have vasoactive properties. To test this hypothesis, we intraarterially infused freshly solubilized A beta 1-40 in rats and observed changes in peripheral blood pressure, cerebral blood flow, and cerebrovascular resistance. We found that infusion of A beta in vivo significantly increased the blood pressure in hypotensive rats but not in normotensive and hypertensive rats. Moreover, A beta infusion also resulted in a decreased blood flow and increased vascular resistance specifically in cerebral cortex but not in heart or kidneys. These data suggest that A beta has a direct and specific constrictive effect on cerebral vessels in vivo, which may contribute to the cerebral hypoperfusion observed early in the AD process.