We utilized 18-month-old endothelial nitric oxide synthase (eNOS) heterozygous knockout (<sup>+/-</sup>) mice, a clinically relevant model of endothelial dysfunction, to examine the role of endothelial nitric oxide (NO) in vascular Aβ accumulation. eNOS<sup>+/-</sup> mice had significantly higher vascular levels of Aβ40 ( P < 0.05).Aβ42 was not detected.