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The APOE-4 Allele and the Risk of Alzheimer Disease Among African Americans, Whites, and Hispanics

Ming-Xin Tang, PhD; Yaakov Stern, PhD; Karen Marder, MD, MPH; Karen Bell, MD; Barry Gurland, MD; Rafael Lantigua, MD; Howard Andrews, PhD; Lin Feng; Benjamin Tycko, MD, PhD; Richard Mayeux, MD, MSc

JAMA. 1998;279:751-755.

Context.— Although the association between Alzheimer disease (AD) and the apolipoprotein E 4 (APOE-4) allele has been confirmed worldwide, it appears to be inconsistent among African Americans, Hispanics, and Nigerians.

Objective.— To investigate the association between the APOE-4 allele and AD in elderly African Americans, Hispanics, and whites.

Design.— Prospective, population-based, longitudinal study over a 5-year period (1991-1996).

Setting.— The Washington Heights–Inwood community of New York City.

Participants.— A total of 1079 Medicare recipients without AD or a related disorder at baseline.

Main Outcome Measures.— Risk of clinically diagnosed AD in the 3 ethnic groups and among individuals with and without an APOE-4 allele.

Results.— Compared with individuals with the APOE-3/3 genotype, the relative risk (RR) of AD associated with 1 or more copies of the APOE-4 allele was significantly increased among whites (RR, 2.5; 95% confidence interval [CI], 1.1-6.4), but not among African Americans (RR, 1.0; 95% CI, 0.6-1.6) or Hispanics (RR, 1.1; 95% CI, 0.7-1.6). In the absence of the APOE-4 allele, the cumulative risks of AD to age 90 years, adjusted for education and sex, were 4 times higher for African Americans (RR, 4.4; 95% CI, 2.3-8.6) and 2 times higher for Hispanics (RR, 2.3; 95% CI, 1.2-4.3) than for whites. In the presence of an APOE-4 allele, the cumulative risk of AD to age 90 years was similar for individuals in all 3 ethnic groups.

Conclusion.— The presence of an APOE-4 allele is a determinant of AD risk in whites, but African Americans and Hispanics have an increased frequency of AD regardless of their APOE genotype. These results suggest that other genes or risk factors may contribute to the increased risk of AD in African Americans and Hispanics.

From the Gertrude H. Sergievsky Center (Drs Tang, Stern, Marder, Bell, and Mayeux), the Taub Center for Alzheimer's Disease Research (Drs Stern, Marder, Bell, Gurland, Lantigua, Andrews, Tycko, and Mayeux and Ms Feng), the Divisions of Biostatistics (Dr Tang) and Epidemiology (Dr Mayeux), School of Public Health, the Departments of Neurology (Drs Stern, Marder, Bell, and Mayeux), Psychiatry (Drs Stern, Gurland, and Mayeux), Medicine (Dr Lantigua), and Pathology (Ms Feng and Dr Tycko), and the Morris W. Stroud III Center for the Study of Quality of Life (Drs Gurland and Lantigua), Columbia University College of Physicians and Surgeons and Columbia-Presbyterian Medical Center, and the Division of Statistics, New York State Psychiatric Institute (Dr Andrews), New York, NY.

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