The APOE-epsilon4 allele and the risk of Alzheimer disease among African Americans, whites, and Hispanics

JAMA. 1998 Mar 11;279(10):751-5. doi: 10.1001/jama.279.10.751.


Context: Although the association between Alzheimer disease (AD) and the apolipoprotein E epsilon4 (APOE-epsilon4) allele has been confirmed worldwide, it appears to be inconsistent among African Americans, Hispanics, and Nigerians.

Objective: To investigate the association between the APOE-epsilon4 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-epsilon4 allele.

Results: Compared with individuals with the APOE-epsilon3/epsilon3 genotype, the relative risk (RR) of AD associated with 1 or more copies of the APOE-epsilon4 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-epsilon4 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-epsilon4 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-epsilon4 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • African Continental Ancestry Group / genetics
  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / ethnology*
  • Alzheimer Disease / genetics*
  • Apolipoproteins E / genetics*
  • European Continental Ancestry Group / genetics
  • Female
  • Gene Frequency
  • Hispanic Americans / genetics
  • Humans
  • Longitudinal Studies
  • Male
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors


  • Apolipoproteins E