Paradoxically, clinical studies suggest an attenuation of APOE ε4 risk of dementia in African ancestry (AFR), but a dearth of neuropathological data preclude the interpretation of the biological factors underlying these findings, including the association between APOE ε4 risk and Alzheimer’s disease (AD) pathology, the most frequent cause of dementia. Here, APOE is linked to early-onset autosomal dominant Alzheimer disease.