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Gene linked to dementia improves cognitive function in carriers with parasitic exposure
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In the Bolivian Amazon, the apolipoprotein E4 allele, which is currently the greatest genetic predictor of Alzheimer’s disease, was associated with improved cognitive function among adults with evidence of a high parasite burden, according to recent study findings.
“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,” Benjamin C. Trumble, PhD, of the School of Human Evolution and Social Change and the Center for Evolution and Medicine at Arizona State University, said in a press release. “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 reported in The FASEB Journal that E4 carriers have a fourfold increased risk for Alzheimer’s disease (AD). Further, E4 is linked to higher total cholesterol and LDL cholesterol, as well as an increased risk for cardiovascular disease in industrialized populations.
“Since E4 contributes to extensive morbidity and mortality worldwide, from an evolutionary perspective, the relatively high worldwide frequency of the E4 allele despite its costs to survivorship is somewhat puzzling,” the researchers wrote.
They noted that previous research has shown that E4 appears to be protective against parasites, which also affect cognitive performance, in endemic environments. For a recent study, the researchers assessed the interactions of E4, parasite burden and cognitive function in a population of forager-horticulturalists in the Bolivian Amazon known as the Tsimane to determine whether E4 protects against cognitive deterioration in a nonindustrialized population with high parasitic exposure. They performed genetic analyses and measured immune markers of infection in 372 participants aged 6 to 88 years. The participants engaged in a 7-part cognitive assessment evaluating cognitive function.
According to the data, 85.9% of participants had eosinophil counts greater than 600 cells/µL, indicating a high parasite load, and approximately 24% were E4 carriers.
E4 carriers aged 30 years and older had reduced cognitive function on most performance measures, which included attention, psychomotor speed, verbal declarative memory and semantic fluency. After controlling for parasite burden, however, the results showed that adults with high eosinophil counts who carried at least one copy of E4 had better cognitive function than noncarriers. The researchers observed a strong interaction between E4 and parasite burden for short- (P = .001) and long-term (P = .013) recall, digit span (P = .097), a composite digit span (P = .051) and a composite fluid task (P = .004). Restricting the cohort to older adults aged 45 to 88 yielded similar results; however, there was no relationship between E4 and parasite load in children.
“Contrary to observations in industrialized populations, older adult E4 carriers with high parasite burdens either maintained or showed slight improvements in cognitive performance, whereas nonE4 carriers with a high parasite burden showed reduced cognitive performance,” Trumble and colleagues wrote.
They concluded that their findings may help to explain the persistence and geographic distribution of E4, which is frequently found in populations residing in areas in tropical latitudes and around the equator.
“This is a wonderful, unanticipated case of a balanced polymorphism affecting a trait, dementia, with predictably major selection consequences,” Thoru Pederson, PhD, editor-in-chief of The FASEB Journal. “Evolution may not work in quite so mysterious ways as delightfully entertaining ways.” – by Stephanie Viguers
Disclosures: Pederson is editor-in-chief of The FASEB Journal. Trumble reports no relevant financial disclosures.
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