Association between angiotensin-converting enzyme and Alzheimer disease

Background: Angiotensin-converting enzyme has been reported to show altered activity in patients with neurologic diseases. An insertion-deletion polym orphism in ACE has recently been linked to heart disease, cerebrovascular d isease, and AD. Objective: To determine whether the angiotensin-converting enzyme (ACE) is associated with risk of Alzheimer disease (AD). Methods: We investigated the ACE polymorphism as a potential risk factor fo r AD in 151 patients with AD and 206 ethnically matched controls from Russi a and in 236 patients with AD and 169 controls from North America by means of allele association methods and logistic regression. Results: None of the ACE genotypes was associated with increased susceptibi lity to AD in the total sample or in subsets stratified by apolipoprotein E gene (APOE) epsilon 4 status. However, the D allele was more frequent amon g AD cases between ages 66 and 70 years compared with controls in both the Russian (P = .02) and North American (P = .001) datasets. In this age group , the effect of D (odds ratio, 11.2, 95% confidence interval, 2.9-44.0) app eared to be independent of and equal or greater in magnitude to the effect of APOE epsilon 4 (odds ratio, 7.8; 95% confidence interval, 3.5-7.4). Conclusions: Our results suggest that APOE and ACE genotypes may be indepen dent risk factors for late-onset AD, but the ACE association needs to be co nfirmed in independent samples in which the time and extent of vascular cof actors can be assessed.