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From the Gertrude H. Sergievsky Center (Drs. Devi, Ottman, Tang, Marder, Stern, and Mayeux); the Departments of Neurology (Drs. Devi, Tang, Marder, Stern, and Mayeux), Psychiatry (Drs. Stern and Mayeux), and Pathology (Dr. Tycko), College of Physicians and Surgeons; the Taub Center for Alzheimer’s Disease Research (Drs. Devi, Tang, Marder, Stern, Tycko, and Mayeux); the Divisions of Epidemiology (Drs. Ottman and Mayeux) and Biostatistics (Dr. Tang), School of Public Health, Columbia University; and the New York State Psychiatric Institute (Drs. Ottman, Stern, and Mayeux), New York, NY.
Address correspondence and reprint requests to Dr. Richard Mayeux, G.H. Sergievsky Center, 630 West 168th Street, New York, NY 10032.
OBJECTIVE: To examine the influence of the proband’s APOE genotype on AD among first-degree relatives in a community-based study of African Americans, whites, and Caribbean Hispanics.
METHODS: History of AD and demographic information were obtained on 1,073 siblings and parents of 312 patients with AD and 2,722 siblings and parents of 802 nondemented controls. APOE genotyping was performed on all 1,114 patients and controls.
RESULTS: A higher proportion of patients with AD (35%) than controls (27%) had one or more APOE-
4 alleles (p = 0.03). When compared with relatives of controls without an APOE-4 allele, the risk for AD was increased in first-degree relatives of both patients (rate ratio [RR] = 1.9, 95% confidence interval [CI] = 1.2 to 3.1) and controls (RR = 1.8, 95% CI = 1.2 to 2.6) with one or more APOE-e alleles, regardless of ethnic group. There was a similar trend of increased risk in relatives of patients without an APOE-4 allele, but this was limited to Hispanics and African Americans.
CONCLUSIONS: The presence of an APOE-4 allele increases risk for AD among first-degree relatives, regardless of the probands’ disease status, among all ethnic groups. Relatives of patients without an APOE-4 allele were also at increased risk for AD among Hispanics and African Americans, suggesting that other genes or risk factors may influence risk.
Key words: AD—Familial aggregation—APOE genotype—Ethnicity.
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