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

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 re
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  1. Victoria says:

    The relationship between APOE4 and diet (cholesterol & calories) seems still under debate, as this study found:

    The dietary habits of 1,032 men aged between 42 and 60 years and with no baseline diagnosis of a cardiovascular disease were assessed at the onset the Kuopio Ischaemic Heart Disease Risk Factor Study, KIHD, in 1984–1989 at the University of Eastern Finland. During a follow-up of 21 years, 230 men had a myocardial infarction, and 32.5 per cent of the study participants were carriers of APOE4.

    The study found that a high intake of dietary cholesterol was not associated with the risk of incident coronary heart disease – not in the entire study population nor in those with the APOE4 phenotype. Moreover, the consumption of eggs, which are a significant source of dietary cholesterol, was not associated with the risk of incident coronary heart disease. The study did not establish a link between dietary cholesterol or eating eggs with thickening of the common carotid artery walls, either.

    The findings suggest that a high-cholesterol diet or frequent consumption of eggs do not increase the risk of cardiovascular diseases even in persons who are genetically predisposed to a greater effect of dietary cholesterol on serum cholesterol levels. In the highest control group, the study participants had an average daily dietary cholesterol intake of 520 mg and they consumed an average of one egg per day, which means that the findings cannot be generalised beyond these levels.

  2. Interesting results that points to the differences in cognitive performance, which depend on the presence of the ApoE4 allele and parasite burden; parasites that apparently are helminths rather than bacteria, protozoa or viruses. Indeed, from what we know about the modulation of the immune response by helminths, these results are what we should expect; i.e. a Th2 anti-inflammatory immunity that protects against cognitive decline. Without discussing the possible mechanisms of protection, the sole Th2 immunity induced by certain helminths glycans that act on the dendritic cell, should avert it likely via protective antibodies while inhibiting inflammation. Yet, in principle that effect should be the same regardless of the presence of E4 or E3 allele, which is not the case here; indeed individuals having the E3 allele did not show improvement with an increasing parasite burden. Actually, the E3 group had a marked cognitive decline that correlated with parasite burden. Hence, these results open the possibility that the effects of some helminth derived products on dementia risk depend on the genotype of the individual. While previously it has been reported that the risk of dementia is decreased by the helminths burden, such study did not address the genetic composition of the different populations. Another intriguing issue is that the protective effect of the antibody aducanumab on cognitive decline is equally effective in individuals having different E alleles, which is not the case in the present study. Thus, it is possible to speculate that under certain conditions, the E allele may be a factor to be considered in the active immune prevention of dementia.

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