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From the Department of Neurology, University of California, San Francisco.
Address correspondence and reprint requests to Dr. J.S. Elkins, Department of Neurology, Box 0114, University of California, San Francisco, 505 Parnassus Ave., M-798, San Francisco, CA 94143-0114; e-mail: elkinsj{at}itsa.ucsf.edu
Background: Numerous studies have tested for associations between common variants of the angiotensin-converting enzyme gene (ACE) and late-onset Alzheimer disease (AD), but results have been inconclusive.
Methods: Relevant studies were systematically identified, and data were abstracted according to predefined criteria.
Results: The odds ratio (OR) for AD in individuals with the I allele of the ACE D/I polymorphism compared with those with the DD genotype was 1.27 (95% CI, 1.10 to 1.47; p < 0.001). Heterogeneity between studies was significant (p < 0.001) but not in strata defined by race and age (p 
0.10). The risk of AD associated with the I allele appeared to be higher among Asians (OR 2.44; 95% CI, 1.68 to 3.53) when compared with the risk among Caucasians (OR 1.18; 95% CI, 1.02 to 1.37) (p for comparison < 0.001), and in younger cases (mean age 65 to 74 years) (OR 1.54; 95% CI, 1.23 to 1.93) when compared with the risk in older cases (OR 1.13; 95% CI, 0.95 to 1.35) (p for comparison = 0.03).
Conclusions: The I allele of the ACE D/I polymorphism is associated with an increased risk of late-onset AD. Further study of the pathogenetic characteristics of this allele and independent confirmation of the association in larger studies are warranted.
Received June 26, 2003. Accepted in final form September 8, 2003.
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