While APOE ε4 allele is considered a genetic risk factor for Alzheimer's disease (AD), no relation existed between APOE ε4 and AD in the Yoruba in Nigeria among cohorts included in early prevalence waves. The authors’ explanation that other disease susceptibilities may provoke earlier mortality is inconsistent with the Yoruba having a lower incidence of disease risk factors. Cohort enrichment in 2001 has altered the authors’ conclusions; Yorba participants homozygous, and not heterozygous, for the ε4 allele had significantly increased risk for AD (HR = 2.95, p = 0.0002) (Hendrie et al., 2014). This is a critical revelation, yet it is not clear why such a temporal relationship exists between risk genotypes and AD among the Yoruba. This letter proposes an explanation.
Epigenomic features related to microglia are associated with attenuated effect of APOE ε4 on Alzheimer’s disease risk in humans