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

• Published in: IDEAS Working Paper Series from RePEc Vol. 10; no. 10:e68231; pp. 1 - 20
• Main Authors: Garcia, Angela R, Finch, Caleb, Gatz, Margaret, Kraft, Thomas, Eid Rodriguez, Daniel, Cummings, Daniel, Charifson, Mia, Buetow, Kenneth, Beheim, Bret A, Allayee, Hooman, Thomas, Gregory S, Stieglitz, Jonathan, Gurven, Michael D, Kaplan, Hillard, Trumble, Benjamin C
• Format: Journal Article Paper
• Language: English
• Published: St. Louis Federal Reserve Bank of St. Louis 29.09.2021; eLife Sciences Publications Ltd; eLife Sciences Publication; eLife Sciences Publications, Ltd
• Subjects: Alzheimer's disease; APOE; Apolipoprotein E4; Apolipoproteins; Biomarkers; Body mass; C-reactive protein; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Costs; Dementia; Economics and Finance; Evolutionary Biology; Humanities and Social Sciences; Hypotheses; Hypothesis testing; Immune response; Infections; Inflammation; Inflammatory diseases; Lipids; Low density lipoprotein; Medicine; Metabolism; Neurological diseases; Obesity; Parasites; Pathogens; Viral infections
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.68231

In post-industrial settings, apolipoprotein E4 (APOE4) 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 APOE4 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 (N = 1266, 50% female), APOE4 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, APOE4 carriers maintain higher levels of total and LDL cholesterol at low body mass indices (BMIs). These results suggest that the relationship between APOE4 and lipids may be beneficial for pathogen-driven immune responses and unlikely to increase cardiovascular risk in an active subsistence population.