The ApoE ε4 Isoform: Can the Risk of Diseases be Reduced by Environmental Factors?

Candidate gene studies and genome-wide association studies found that genetic variation in APOE is robustly associated with multiple age-related diseases and longevity. Apolipoprotein E (ApoE) is an apolipoprotein that plays an important role in triglyceride and cholesterol metabolism. In literature, especially the ApoE ɛ4 isoform has been associated with an increased risk of mortality and age-related diseases such as Alzheimer's disease (AD), cardiovascular diseases (CVD), as compared to the "neutral" ApoE ɛ3 isoform. There are, however, large differences in the deleterious effects of the ApoE ɛ4 isoform between ancestries and populations, which might be explained by differences in environmental and lifestyle exposures. In this respect, poor nutrition and physical inactivity are two important lifestyle factors that have been associated with increased risks for AD and CVD. Therefore, in this narrative review, we discuss how omega-3 fatty acid intake and physical activity may modify the impact of ApoE ɛ4 on AD and CVD risk.