Apolipoprotein E and Alzheimer's disease pathology in a diverse autopsy study.

INTRODUCTION: Apolipoprotein E allele 4 (APOE ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD), but most evidence comes from White populations in high-income countries. We investigated APOE and AD pathology in an ethnically diverse Brazilian autopsy cohort. METHODS: This cross-sectional study used Biobank for Aging Studies (BAS) data. AD pathology was evaluated with Braak, Consortium to Establish a Registry for Alzheimer's Disease, and Thal criteria. APOE genotypes were obtained from blood or brain tissue. Regression models were adjusted for age, sex, race, and education; interaction with race was tested. RESULTS: Among 1391 participants (mean age 75.1 ± 12.4 years, 50% women, 64% White), APOE ε4showed a dose response with greater AD pathological burden and higher odds of AD diagnosis, while APOE ε2/X was protective. APOE ε4/ε4 did not show full penetrance across age groups. Associations were similar in White and Black individuals. DISCUSSION: APOE ε4was strongly associated with AD pathology, with consistent associations across racial groups. HIGHLIGHTS: APOE ε4 increased AD neuropathological burden in Brazilians. APOE ε2/εX was protective against AD pathology. APOE ε4/ε4did not show full penetrance across age groups. Associations between APOE and AD pathology were similar by race. Large multiethnic autopsy study expands evidence beyond high-income country studies.