Apoe4 is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical amerindian subsistence population

• Type of Material: Article
• Authors: Angela R Garcia, Emory University; Caleb Finch, University of Southern California; Margaret Gatz, University of Southern California; Thomas Kraft, University of California, Santa Barbara; Daniel Eid Rodriguez, Universidad Mayor de San Simón; Daniel Cummings, Chapman University; Mia Charifson, New York University; Kenneth Buetow, Arizona State University; Bret A Beheim, Max-Planck-Institut für evolutionäre Anthropologie; Hooman Allayee, Keck School of Medicine of USC; Gregory S Thomas, University of California, Irvine; Jonathan Stieglitz, Université Fédérale Toulouse Midi-Pyrénées; Michael D Gurven, University of California, Santa Barbara; Hilard Kaplan, Chapman University; Benjamin C Trumble, Arizona State University
• Language: English
• Date: 2021-09-01
• Publisher: Emory University Libraries
• Publication Version: Final Published Version
• Copyright Statement: © 2021, Garcia et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.7554/eLife.68231
• Title of Journal or Parent Work: eLife
• Volume: 10
• Grant/Funding Information: National Institute on Aging R56AG024119 to Michael D Gurven.; Agence Nationale de la Recherche to Jonathan Stieglitz.; National Institute on Aging R01AG024119 to Michael D Gurven, Hillard Kaplan.; This paper was supported by the following grants:
• Keywords: Genotype; Indians, South American; inflammation; medicine; Apolipoprotein E4; APOE; Male; Middle Aged; Humans; Female; human; Alzheimer's disease; evolutionary biology; Diet; Tropical Climate; Bolivia; dementia; Immunity, Innate; Lipids; Obesity; Risk Factors; Life Style; cardiovascular disease; cholesterol; Biomarkers; Body Mass Index
• Research Categories: Health Sciences, Medicine and Surgery; Anthropology, Medical and Forensic

Abstract

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 hypoth-esize 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 bene-ficial for pathogen-driven immune responses and unlikely to increase cardiovascular risk in an active subsistence population.