Summary: A new study asks whether a genetic variant tied to neurodegeneration in modern settings might provide benefits in different, infection-rich environments.
Source: Arizona State University.
Study finds cognitive decline may depend on the interaction between genes and environment — even parasites.
We often talk about being in the right place at the wrong time. This study considers the inverse: might a gene variant that increases disease risk in one environment be advantageous in another? Researchers explored whether the apolipoprotein E variant known as ApoE4, widely studied in industrialized populations for its link to Alzheimer’s disease and cardiovascular risk, could act differently in a traditional, pathogen-rich environment.
The work, led by Benjamin Trumble of Arizona State University’s School of Human Evolution and Social Change and ASU’s Center for Evolution and Medicine, appears in FASEB Journal. The team focused on the Tsimane, an Amazonian forager-horticulturalist population that lives with high exposure to parasites and infectious agents due to limited sanitation and infrastructure. These conditions resemble the environments in which humans lived for most of our species’ history.
Apolipoprotein E (ApoE) proteins play key roles in cholesterol metabolism and transport of fatty acids to the brain. In post-industrial populations, carrying the ApoE4 allele is associated with up to a fourfold increase in risk for Alzheimer’s disease and accelerated age-related cognitive decline, as well as elevated cardiovascular risk. Given that many equatorial and traditional populations have comparatively high frequencies of ApoE4, the researchers asked whether ApoE4 might function differently where infectious burden is high.
Contrary to expectations based on industrialized cohorts, the study found that among older Tsimane adults with heavy parasite burdens, ApoE4 carriers maintained cognitive performance better than non-carriers with similar infection levels. The research team assessed 372 individuals from the Tsimane Health and Life History Project using a seven-part cognitive battery and medical examinations. After controlling for age, education, and other potential confounders, ApoE4 carriers with high parasite loads showed stable or slightly improved cognitive scores, whereas non-carriers with high parasite loads showed reduced cognitive performance.
By contrast, Tsimane ApoE4 carriers who did not have high parasite burdens exhibited patterns of cognitive decline more consistent with findings from industrialized populations, where ApoE4 is generally linked to worse cognitive outcomes. These results suggest an interaction between genetic background and the infectious environment: the same allele associated with late-life cognitive risk in sanitized, industrial settings may confer advantages when infectious pressures are high.
Lead author Trumble notes the importance of environmental context for interpreting genetic effects: for the vast majority of human evolutionary history, people lived as hunter-gatherers or in small-scale agricultural communities, not within the sanitized, sedentary environments common today. Traits that were advantageous in pathogen-rich or resource-variable settings may now be mismatched to modern lifestyles.
The study also highlights that ApoE4 is not solely a deleterious relic. Other work has linked ApoE4 to potential benefits in early development and to enhanced resistance against certain infections such as giardia and hepatitis. Evolutionary theory predicts that alleles producing harm late in life can persist if they provide benefits earlier in life or under particular environmental conditions. This trade-off may help explain why ApoE4 remains common in some populations.
Michael Gurven, a co-author and professor of anthropology, emphasizes that examining disease-associated genes across a wider range of ecological settings—especially those with higher infectious exposures—can clarify why alleles often labeled “bad genes” persist globally. The apparent advantage of ApoE4 for cognitive function under high parasite burden suggests that the relationship between genotype and health is context-dependent.
Source: Aaron Pugh, Arizona State University.
Image source: NeuroscienceNews image used for illustration.
Original research: Trumble BC, Stieglitz J, Blackwell AD, Allayee H, Beheim B, Finch CE, Gurven M, Kaplan H. “Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden.” FASEB Journal. Published online December 28, 2016. doi:10.1096/fj.201601084R
Abstract
Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden
The ApoE4 allele is found worldwide despite its links to greater cardiovascular morbidity, accelerated cognitive decline with aging, and Alzheimer’s disease. Some tropical populations show relatively high E4 prevalence along with elevated parasite burdens that can independently impair cognition. This study examined interactions among ApoE4, parasite burden, and cognitive performance in a traditional, nonindustrial Amazonian population (N = 372) to test whether ApoE4 offers protection against cognitive decline where pathogens are common. Contrary to findings from industrialized populations, older E4 carriers with high parasite loads either maintained or slightly improved cognitive performance, while non-E4 carriers with high parasite loads showed reduced cognitive performance. Although ApoE4 is the strongest genetic risk factor identified so far for Alzheimer’s disease and cognitive decline in industrial populations, in environments with heavy parasite and pathogen loads it appears associated with better cognitive outcomes, suggesting context-dependent advantages. The mismatch between modern hygienic lifestyles and historically common parasite-rich environments may be important for understanding genetic risk for cognitive aging.
“Apolipoprotein E4 is associated with improved cognitive function in Amazonian forager-horticulturalists with a high parasite burden” by Benjamin C. Trumble, Jonathan Stieglitz, Aaron D. Blackwell, Hooman Allayee, Bret Beheim, Caleb E. Finch, Michael Gurven and Hillard Kaplan. FASEB Journal. Published online December 28, 2016. doi:10.1096/fj.201601084R