The Proportion of APOE4 Carriers Among Non-Demented Individuals: A Pooled Analysis of 389,000 Community-Dwellers.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of observational studies.
PubMed 33935087 · doi:10.3233/JAD-201606
What was done
Authors searched PubMed, EMBASE, and CNKI through April 20, 2020, for community-based studies reporting APOE polymorphisms with at least 500 non-demented participants. Proportions of APOE4 carriers (2/4, 3/4, or 4/4) were pooled using random-effects models. Meta-regression and subgroup analyses assessed heterogeneity, and age-standardized pooled proportion estimates were derived via direct standardization.
What was found
A total of 121 studies across 38 countries (pooled sample of ~389,000 community-dwellers) were included: - Global average proportion of APOE4 carriers was 23.9% (age-standardized: 26.3%). - Subtype proportions: 20.6% for APOE3/4, 2.3% for APOE2/4, and 2.1% for APOE4/4. - Significant geographical variation (19.3% to 30.0%, p < 0.0001): highest in Africa, followed by Europe, North America, Oceania, and lowest in South America and Asia. - Significant ethnic variation (19.1% to 37.5%, p < 0.0001): highest in Africans, followed by Caucasians, and lowest in Hispanics/Latinos and Chinese.
Why it matters
It provides large-scale benchmark estimates of APOE4 carriage among cognitively normal individuals globally, essential for precision medicine, epidemiological modeling, and Alzheimer's disease clinical trial enrichment.
Limits
Studies with fewer than 500 participants were excluded, potentially introducing selection bias and omitting smaller regional populations. The abstract does not report confidence intervals, risk-of-bias assessments, or the specific screening instruments used across original studies to confirm non-demented status.
Cited by
- supports Many people who carry the APOE4 allele do not develop Alzheimer's disease, and many people with Alzheimer's disease do not carry the APOE4 allele.