Abstract: Objective. —To examine more closely the association between apolipoprotein E (APOE) genotype and Alzheimer disease (AD) by age and sex in populations of various ethnic and racial denominations. Data Sources. —Forty research teams contributed data onAPOEgenotype, sex, age at disease onset, and ethnic background for 5930 patients who met criteria for probable or definite AD and 8607 controls without dementia who were recruited from clinical, community, and brain bank sources. Main Outcome Measures. —Odds ratios (ORs) and 95% confidence intervals (Cls) for AD, adjusted for age and study and stratified by major ethnic group (Caucasian, African American, Hispanic, and Japanese) and source, were computed forAPOEgenotypes ∈2/∈2,∈2/∈3,∈2/∈4,∈3/∈4 and ∈4/∈4 relative to the ∈3/∈3 group. The influence of age and sex on the OR for each genotype was assessed using logistic regression procedures. Results. —Among Caucasian subjects from clinic- or autopsy-based studies, the risk of AD was significantly increased for people with genotypes ∈2/∈4 (OR=2.6, 95% Cl=1.6-4.0), ∈3/∈4 (OR=3.2, 95% Cl=2.8-3.8), and ∈4/∈4 (OR=14.9, 95% CI=10.8-20.6); whereas, the ORs were decreased for people with genotypes ∈2/∈2 (OR=0.6, 95% Cl=0.2-2.0) and ∈2/∈3 (OR=0.6, 95% Cl=0.5-0.8). TheAPOE∈4-AD association was weaker among African Americans and Hispanics, but there was significant heterogeneity in ORs among studies of African Americans (P Conclusions. —TheAPOE∈4 allele represents a major risk factor for AD in all ethnic groups studied, across all ages between 40 and 90 years, and in both men and women. The association betweenAPOE∈4 and AD in African Americans requires clarification, and the attenuated effect ofAPOE∈4 in Hispanics should be investigated further.
... read more