<i>APOE4</i> is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical Amerindian subsistence population.

Abstract

In post-industrial settings, apolipoprotein <i>E4</i> (<i>APOE4</i>) is associated with increased cardiovascular and neurological disease risk. However, the majority of human evolutionary history occurred in environments with higher pathogenic diversity and low cardiovascular risk. We hypothesize that in high-pathogen and energy-limited contexts, the <i>APOE4</i> allele confers benefits by reducing innate inflammation when uninfected, while maintaining higher lipid levels that buffer costs of immune activation during infection. Among Tsimane forager-farmers of Bolivia (<i>N</i> = 1266, 50% female), <i>APOE4</i> is associated with 30% lower C-reactive protein, and higher total cholesterol and oxidized LDL. Blood lipids were either not associated, or negatively associated with inflammatory biomarkers, except for associations of oxidized LDL and inflammation which were limited to obese adults. Further, <i>APOE4</i> carriers maintain higher levels of total and LDL cholesterol at low body mass indices (BMIs). These results suggest that the relationship between <i>APOE4</i> and lipids may be beneficial for pathogen-driven immune responses and unlikely to increase cardiovascular risk in an active subsistence population.