The apolipoprotein E4 (E4) allele is present worldwide. Its presence is associated with higher risk of cardiovascular morbidity, accelerated cognitive decline during aging, and Alzheimer's disease (AD).
‘Under certain environmental conditions especially in tropical zones where parasitic burden is high, apolipoprotein E4 allele may reduce the risk of associated cognitive decline.’
It is the strongest genetic predictor of Alzheimer's disease.
In some tropical regions, the E4 allele is especially prevalent along with a high parasite burden. Equatorial populations also face a potential dual burden of high E4 prevalence combined with parasitic infections.
Parasitic infections can also reduce cognitive performance.
This protective effect of E4 allele 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 added.
Studying the Role of E4 Allele
The remote population of forager-horticulturalists in the Bolivian Amazon, called the Tsimane experience high parasite loads, making them a suitable population for studying the role of the E4 allele in this circumstance.
Researchers examined cognitive performance and parasite exposure data from 372 Tsimane men and women aged 6-88 years. .
The researchers undertook a genetic analysis, measured immune markers of parasitic infection, and conducted cognitive tests.
They found that for those men and women, who had a larger parasitic load and did not carry the E4 allele, experienced poorer cognitive performance.
On the other hand, those who carried the E4 allele, 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."
The new research is published online in The FASEB Journal
- Benjamin C. Trumble et al. Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden. The FASEB Journal; (2016) doi:10.1096/fj.201601084Rfj.201601084R