Cerebrovascular endothelial dysfunction mediated by beta-amyloid.

beta-Amyloid (A beta) toxicity has a critical role in the pathology of Alzheimer's disease (AD) but its function in the neurodegenerative process is not clearly established. Recently, we demonstrated a novel action of beta-amyloid on peripheral blood vessels: endothelial dysfunction through reactive oxygen species. Here we report the direct effect of A beta on cerebrovascular endothelium. Following treatment with A beta 1-40, bovine cerebral arteries showed characteristic features of endothelial dysfunction such as increased contraction to vasoconstrictor and diminished relaxation to endothelium-dependent vasodilators. Electron microscopy revealed significant damage to the endothelium by A beta. Pretreatment with the antioxidant superoxide dismutase (SOD) and PBN (n-tert-butyl-alpha-phenylnitrone) antagonized the effects of A beta. Endothelial damage induced by A beta could produce ischemic and inflammatory changes contributing to the pathology of AD.