Gene Variant Tied to Cognitive Decline Can Be Beneficial, Depending on Where You Live

Cognitive decline can be triggered by the ApoE4 gene variant, but that trigger depends on environmental factors, a new study reports. This finding supports the idea that certain diseases, such as Alzheimer’s, are influenced by the interaction between a person’s genes and environment.

The study, “Apolipoprotein E4 Is Associated with Improved Cognitive Function In Amazonian Forager-Horticulturalists With A High Parasite Burden,” was published in The FASEB Journal.

ApoE proteins help regulate the levels of cholesterol in the blood and transport fat molecules to the brain. However, high levels of the ApoE4 variant (one of the possible versions of the ApoE gene) are associated with an increased risk of heart disease, accelerated cognitive decline during aging, and Alzheimer’s disease. People in industrialized countries, where highly caloric food is available at all times, have high levels of the ApoE4 variant and, thus, higher risk of developing Alzheimer’s and other cognitive conditions associated with aging.

“For 99 percent of human evolution, we lived as hunter-gatherers in small bands, and the last 5,000-10,000 years — with plant and animal domestication and sedentary urban industrial life — is completely novel,” Ben Trumble, the study’s first author, said in a news release. “I can drive to a fast-food restaurant to ‘hunt and gather’ 20,000 calories in a few minutes or go to the hospital if I’m sick, but this was not the case throughout most of human evolution.”

People in tropical regions are thought to have high levels of ApoE4 caused by parasitic infections, and subsequently may also be at an increased risk of cognitive decline. Parasitic infections are frequent in tropical environments, and also in areas marked by a lack of sanitation, running water or electricity. If not properly treated, parasitic infections can cause brain damage.

Researchers analyzed whether the ApoE4 variant affected people in remote and tropical areas, such as the Tsimane (Amazonian forager-horticulturalists), differently from people in developed countries.

They expected that Tsimane individuals with high levels of ApoE4 and high parasite burden would have a faster cognitive decline.

But the results were quite surprising, showing Tsimane populations with these features had more stable or even improved cognitive function compared to those with high parasitic burden only. Members of this Amazonian group who were not exposed to parasitic infections but had high levels of the ApoE4 variant showed rates of cognitive decline similar to that observed in industrialized countries.

These results suggest that the influence of ApoE4 may depend on the environment that surrounds the individual: it contributes to cognitive loss in people living in industrialized societies, but helps to maintain cognitive function in people exposed to health threats, such as parasites.

“It seems that some of the very genetic mutations that help us succeed in more hazardous time periods and environments may actually become mismatched in our relatively safe and sterile post-industrial lifestyles,” said Trumble.

According to the researcher, the ApoE4 variant may not be something the evolution “forgot” to get rid of when it was no longer necessary, but rather a player in several processes, such as development in early childhood and protection against hepatitis and giardia, an infection-causing parasite.

“[Variants] with harmful effects may remain in a population if such harm occurs late in life, and more so if those same alleles have other positive effects,” said Michael Gurven, a study author. “Exploring the effects of genes associated with chronic disease, such as ApoE4, in a broader range of environments under more infectious conditions is likely to provide much-needed insight into why such ‘bad genes’ persist.”