‘Dementia gene’ may guard against decline associated with parasitic disease

New research published online in The FASEB Journal, suggests that carriers of the Apolipoprotein E4 allele, which is the single strongest genetic predictor of Alzheimer's disease and is associated with cognitive decline and cardiovascular disease, may have a reduced risk of cognitive decline associated with parasitic diseases. This protective effect may help explain why this "disease" gene has persisted over the millennia, as well as offering insights into preventing and treating the cognitive problems caused by human parasites.

"While being an E4 carrier is the strongest risk factor to date of Alzheimer's dementia and cognitive decline in industrial populations, it is associated with greater cognitive performance in individuals facing a high parasite and pathogen load, suggesting advantages to the E4 allele under certain environmental conditions," said Benjamin C. Trumble, Ph.D., a researcher involved in the work at the School of Human Evolution and Social Change and the Center for Evolution and Medicine at Arizona State University in Tempe, Arizona. "The current mismatch between sedentary postindustrial lifestyles and active parasite-rich lifeways experienced throughout most of human history may be critical for understanding genetic risk for cognitive aging."

Trumble and colleagues examined cognitive performance and parasite exposure data from a remote population of forager-horticulturalists in the Bolivian Amazon, called the Tsimane. The Tsimane experience high parasite loads, making them a suitable population for study for the role of the E4 allele in this circumstance. The researchers undertook a genetic analysis, measured immune markers of parasitic infection, and conducted cognitive tests on 372 Tsimane men and women aged 6 to 88 years. They found that for the Tsimane who did not carry the E4 allele, a larger parasite burden resulted in poorer cognitive performance. Those who carried the E4 allele, however, maintained cognitive performance even with very high parasite burdens.

"This is a wonderful, unanticipated case of a balanced polymorphism affecting a trait, dementia, with predictably major selection consequences" said Thoru Pederson, Ph.D., Editor-in-Chief of The FASEB Journal. "Evolution may not work in quite so mysterious ways as delightfully entertaining ways."

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Submit to The FASEB Journal by visiting http://fasebj.msubmit.net, and receive monthly highlights by signing up at http://www.faseb.org/fjupdate.aspx. The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB). It is the world's most cited biology journal according to the Institute for Scientific Information and has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century.

FASEB is composed of 30 societies with more than 125,000 members, making it the largest coalition of biomedical research associations in the United States. Our mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.

Details: Benjamin C. Trumble, Jonathan Stieglitz, Aaron D. Blackwell, Hooman Allayee, Bret Beheim, Caleb E. Finch, Michael Gurven, and Hillard Kaplan. Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden. FASEB J. doi:10.1096/fj.201601084R ; http://www.fasebj.org/content/early/2017/01/03/fj.201601084R.abstract

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