The relationship between APOE and vessel-associated NEP activity mirrored that between APOE genotype and risk of AD and CAA: after adjustment for smooth muscle actin, NEP activity was highest in blood vessels from patients with APOE ε2/3 genotype and decreased stepwise through APOE ε3/3, ε3/4, and ε4/4 genotypes. Here, APOE is linked to Alzheimer disease.