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The association between apolipoprotein E (APOE)-epsilon 4 and Alzheimer's disease has been confirmed worldwide. We and others have observed a diminished association in the very old and among African-Americans compared to Caucasians and Hispanics in New York. In this review we describe a new method we developed to compare relative risks by APOE genotypes in an expanded cohort of cases and controls from three ethnic groups in a New York City community and discuss the association as between APOE epsilon 4 and Alzheimer's disease as modified by head injury. Compared to persons with APOE epsilon 3/epsilon 3 genotypes, relative risk (RR) for Alzheimer's disease associated with APOE epsilon 4 homozygosity was similar across ethnic groups (African-American RR = 3.3; 95% c.i. 1.6-6.8; Caucasian RR = 5.3; 1.6-16.0; Hispanic RR = 2.5; 1.1-5.8). The risk was also increased for APOE epsilon 4 heterozygous Caucasians (RR = 3.2; 1.8-5.8) and Hispanics (RR 1.5; 1.0-2.2) but not African-Americans (RR = 0.6; 0.4-0.9). Risk of AD was not significantly diminished for individuals in any group with APOE epsilon 2/epsilon 2 or -epsilon 2/epsilon 3 genotypes. A 10-fold increase in the risk of Alzheimer's disease was associated with both APOE epsilon 4 and a history of traumatic head injury, compared to a twofold increase in risk with APOE epsilon 4 alone. Head injury in the absence of an APOE epsilon 4 allele did not increase risk. These results imply that in Alzheimer's disease genotypic risk associated with APOE may be influenced by age, ethnicity, and certain environmental factors.
TANG et al. (Sun,) studied this question.