Aging enhances vascular dysfunction induced by the Alzheimer's peptide β-amyloid

Abstract

Aging is a major risk factor for Alzheimer's disease and the evidence suggests a role for cerebrovascular pathology in cognitivedysfunction. The hypothesis in this study is that aging is a significant risk factor in the effect of the Alzheimer peptide β-amyloid on endothelium-dependent function of cerebral and peripheral vessels. The diameter response to acetylcholine, an endothelium-dependent vasodilator, was recorded in pressurized segments of rat posterior cerebral vessels from mature (3 months) and aged (20 months) rats. The threshold concentration of β-amyloid for a significant decrease in the response to acetylcholine was lower in vessels from aged rats (10-9 M) than in vessels from mature rats (10-8 M). The threshold concentration of β-amyloid for a significant decrease in the sensitivity to acetylcholine was lower for ring segments of aorta from aged rats (10-10 M) than for aorta from mature rats (10-8 M). Structural changes of the endothelium were first observed in electron micrographs of aorta from aged rats when the concentration of β-amyloid was 10-8 M, whereas structural changes in aorta from mature rats did not occur until the concentration of β-amyloid was increased to 10-7 M. The results suggest that aging increases the susceptibility of cerebral and peripheral blood vessels to β-amyloid related dysfunction and that functional change precedes structural change.