Associations of APOE Genetic Isoforms with Longevity and Risk of Mortality in Human Populations

Prior to the age of 60 life expectancy is minimally impacted by hereditary factors; however, this influence becomes more pronounced in older age groups. It is crucial to elucidate the relationship between some genetic variants, life expectancy, and susceptibility to age-related diseases, particularly within the context of the genetic diversity present among human populations inhabiting various environmental conditions. Among genetic factors the apolipoprotein E (APOE) gene merits particular attention. This review examines the role of different APOE alleles and genotypes in relation to late age attainment and their associations with longevity across various human populations. The ε4 allele is a well-established genetic risk factor for Alzheimer’s disease (AD) among Eurasian populations, and its prevalence is significantly lower in most longevity groups compared to the general population. Conversely, the rarer ε2 allele is associated with a reduced risk of AD and is more frequently observed in longevity groups than in healthy middle-aged individuals. It would be interesting to determine whether the differential representation of APOE alleles in long-lived individuals, as compared to the general population, is influenced by the effect of APOE on the risk of AD or other diseases. Furthermore, the role of the APOE genotype in reaching late age among African populations, where a robust association between the ε4 allele and AD has not been conclusively established, warrants further examination. This review also addresses the biological age at which the ε4 and ε2 alleles significantly affect mortality risk, as well as the influence of genetic factors that may either exacerbate or mitigate the effects of the ε4 allele on associated life expectancy.