Race-Related Association between APOE Genotype and Alzheimer's Disease: A Systematic Review and Meta-Analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational case-control studies
PubMed 34334408 · doi:10.3233/JAD-210549
What was done
Authors systematically reviewed PubMed, Embase, Web of Science, and Cochrane Library records from 1993 to August 25, 2020. They identified 133 eligible studies comprising 77,402 participants with clinical Alzheimer's disease (AD) diagnostic and APOE genotype data. Homogeneous datasets were pooled in case-control meta-analyses to calculate odds ratios and 95% confidence intervals across different races, APOE genotypes, and AD onset age (early-onset vs. late-onset).
What was found
The abstract reports no numerical effect sizes, odds ratios, or confidence intervals. Directionally, APOE ε4 was identified as a risk factor for AD, whereas APOE ε2 was protective. The magnitude of these associations varied across races and was substantially attenuated among Black individuals. Early-onset AD showed a higher frequency of APOE ε4/ε4 and lower frequency of APOE ε3/ε3 compared to late-onset AD in combined and race-stratified groups.
Why it matters
This meta-analysis demonstrates that APOE genotype-associated risk for Alzheimer's disease differs by race, cautioning against generalizing genetic risk estimates derived predominantly from single ancestral populations.
Limits
The abstract provides no effect sizes, confidence intervals, p-values, or heterogeneity statistics. Included primary studies were observational case-control designs subject to selection bias, potential misclassification of clinical AD diagnoses, and unmeasured confounding related to genetic admixture within broadly defined racial categories.
Cited by
- supports Carrying one or two copies of the APOE2 allele strongly protects against developing Alzheimer's disease.