Ancient protective DNA ups Alzheimer's risk in modern humans

Washington: A gene mutation that protected ancient hunter-gatherers from cognitive decline may have become mismatched in our modern sterile lifestyles, making us prone to the risk of diseases like Alzheimer's, a new study has found.

Researchers at Arizona State University in the US examined how the apolipoprotein E (ApoE) gene might function differently in an infectious environment than in the urban industrialised settings where it has mostly been examined. All ApoE proteins help mediate cholesterol metabolism, and assist in the crucial activity of transporting fatty acids to the brain.

However, in industrialised societies, ApoE4 variant carriers also face up to a four-fold higher risk for Alzheimer's disease and other age-related cognitive declines, as well as a higher risk for cardiovascular disease. Researchers wanted to examine the potentially detrimental effects of the ApoE4 allele in environmental conditions experienced throughout our species' existence.

"For 99 per cent 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," said lead author Ben Trumble. "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," he said.

Due to the tropical environment and a lack of sanitation, running water, or electricity, remote populations like a community of Amazonian forager-horticulturalists called the Tsimane face high exposure to parasites and pathogens, which cause their own damage to cognitive abilities when untreated.
As a result, one might expect Tsimane ApoE4 carriers who also have a high parasite burden to experience faster and more severe mental decline in the presence of both these genetic and environmental risk factors.

However researchers found that those Tsimane who carried ApoE4 and had a high parasitic burden displayed steadier or improved cognitive function. This indicated that the allele potentially played a role in maintaining cognitive function even when exposed to environmental-based health threats.

For Tsimane ApoE4 carriers without high parasite burdens, the rates of cognitive decline were more similar to those seen in industrialised societies, where ApoE4 reduces cognitive performance. "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," Trumble said.

For example, several studies have shown potential benefits of ApoE4 in early childhood development. ApoE4 has also been shown to eliminate some infections like giardia and hepatitis. The research was published in The FASEB Journal.