Genetic flaw tied to Alzheimer's was not always so bad

A gene mutation linked to Alzheimer's disease and other age-related cognitive declines in our relatively safe and sterile post-industrial setting might have actually helped protect us from cognitive decline in ancient times, a new research suggests.

The findings suggest that a genetic mutation (or allele) that puts populations at risk for illnesses in one environmental setting could manifest itself in positive ways in a different setting.

"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 lead author Ben Trumble, Assistant Professor at the Arizona State University in the US.

In a paper published in The FASEB Journal, the researchers examined how the apolipoprotein E (ApoE) gene might function differently in an infectious environment than in the urban industrialised settings where ApoE has mostly been examined.

All ApoE proteins help mediate cholesterol metabolism, and assist in the crucial activity of transporting fatty acids to the brain. But 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.

The goal of this study was to reexamine the potentially detrimental effects of the globally-present ApoE4 allele in environmental conditions more typical of those experienced throughout our species' existence in this case, a community of Amazonian forager-horticulturalists called the Tsimane.

"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," Trumble said.

Due to the tropical environment and a lack of sanitation, running water, or electricity, remote populations like 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. But researchers discovered the exact opposite when they tested these individuals using a seven-part cognitive assessment and a medical exam.

In fact, Tsimane who both carried ApoE4 and had a high parasitic burden displayed steadier or even improved cognitive function in the assessment versus non-carriers with a similar level of parasitic exposure. This indicated that the allele potentially played a role in maintaining cognitive function even when exposed to environmental-based health threats.