Effect of age, ethnicity, and head injury on the association between APOE genotypes and Alzheimer's disease

Abstract

The association between apolipoprotein E (APOE)-ε4 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 ε4 and Alzheimer's disease as modified by head injury. Compared to persons with APOE ε3/ε3 genotypes, relative risk (RR) for Alzheimer's disease associated with APOE ε4 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 ε4 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 ε2/ε2 or -ε2/ε3 genotypes. A 10-fold increase in the risk of Alzheimer's disease was associated with both APOE ε4 and a history of traumatic head injury, compared to a twofold increase in risk with APOE ε4 alone. Head injury in the absence of an APOE ε4 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 enviromental factors.