The Proportion of APOE4 Carriers Among Non-Demented Individuals: A Pooled Analysis of 389,000 Community-Dwellers.

BACKGROUND The apolipoprotein E epsilon 4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Its carriage percentage in non-demented population varies across geographic regions and ethnic groups. OBJECTIVE To estimate the proportion of APOE4 (2/4, 3/4, or 4/4) carriers in non-demented community-dwellers. METHODS PubMed, EMBASE, and China National Knowledge Infrastructure were searched from inception to April 20, 2020. Community-based studies that reported APOE polymorphisms with a sample of≥500 non-demented participants were included. Random-effects models were used to pool the results. Meta-regression and subgroup analyses were performed to test the source of heterogeneity and stratified effects. Age-standardized pooled proportion estimates (ASPPE) were calculated by direct standardization method. RESULTS A total of 121 studies were included, with a pooled sample of  389,000 community-dwellers from 38 countries. The global average proportion of APOE4 carriers was 23.9% (age-standardized proportion: 26.3%; 2.1% for APOE4/4, 20.6% for APOE3/4 and 2.3% for APOE2/4), and varied significantly with geographical regions (from 19.3% to 30.0%) and ethnic groups (from 19.1% to 37.5%). The proportion was highest in Africa, followed by Europe, North America, Oceania, and lowest in South America and Asia (p <  0.0001). With respect to ethnicity, it was highest in Africans, followed by Caucasians, and was lowest in Hispanics/Latinos and Chinese (p <  0.0001). CONCLUSION APOE4 carriers are common in communities, especially in Africans and Caucasians. Developing precision medicine strategies in this specific high-risk population is highly warranted in the future.