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Association Between Angiotensin-Converting Enzyme and Alzheimer Disease
Lindsay A. Farrer, PhD;
Tatyana Sherbatich;
Sergey A. Keryanov, PhD;
Galina I. Korovaitseva, PhD;
Ekaterina A. Rogaeva, PhD;
Svetlana Petruk, PhD;
Smita Premkumar, PhD;
Yuri Moliaka, PhD;
You Qiang Song, PhD;
York Pei, MD;
Christine Sato;
Natalya D. Selezneva, MD;
Svetlana Voskresenskaya, MD;
Vera Golimbet, PhD;
Sandro Sorbi, MD;
Rangene Duara, MD;
Svetlana Gavrilova, MD;
Peter H. St. George-Hyslop, MD;
Evgeny I. Rogaev, PhD
Arch Neurol. 2000;57:210-214.
Background Angiotensin-converting enzyme has been reported to show altered activity in patients with neurologic diseases. An insertion-deletion polymorphism in ACE has recently been linked to heart disease, cerebrovascular disease, 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 for AD in 151 patients with AD and 206 ethnically matched controls from Russia 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 susceptibility to AD in the total sample or in subsets stratified by apolipoprotein E gene (APOE)  4 status. However, the D allele was more frequent among 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) appeared to be independent of and equal or greater in magnitude to the effect of APOE 4 (odds ratio, 7.8; 95% confidence interval, 3.5-7.4).
Conclusions Our results suggest that APOE and ACE genotypes may be independent risk factors for late-onset AD, but the ACE association needs to be confirmed in independent samples in which the time and extent of vascular cofactors can be assessed.
From the Departments of Medicine (Genetics Program) (Drs Farrer and Premkumar) and Neurology (Dr Farrer), Boston University School of Medicine, and Department of Epidemiology and Biostatistics, Boston University School of Public Health (Dr Farrer), Boston, Mass; Mental Health Research Center (Ms Sherbatich and Drs Keryanov, Korovaitseva, Petruk, Moliaka, Selezneva, Voskresenskaya, Golimbet, Gavrilova, and Rogaev) and Center of Medical Genetics (Dr Moliaka), Russian Academy of Medical Sciences, Moscow, Russia; Centre for Research in Neurodegenerative Diseases, Department of Medicine, University of Toronto, and Division of Neurology, Department of Medicine, The Toronto Hospital, Toronto, Ontario (Drs Rogaeva, Song, Pei, and St. George-Hyslop and Ms Sato); Department of Neurology and Psychiatry, University of Florence, Firenze, Italy (Dr Sorbi); and University of Miami School of Medicine, Miami, Fla (Dr Duara).
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