Apoe4 – the Ancestral allele

APOE4 (A4) carriers, especially homozygotes (carry 2 copies of the APOE4 allele, A4/4s) are considered to have a genetic predisposition to a shortened life-span, cardiovascular disease, and most notoriously, to Alzheimer’s disease (up to 12x the risk). Because of this, A4 has been dubbed the Alzheimer’s gene, with some going as far as calling it the Death gene. These dire references have many folks terrified to learn their A4 status and by not doing so, they may miss out on windows of opportunity to mitigate risk.

I argue that referring to A4 as the Alzheimer’s or Death gene is egregiously inappropriate because:

1. Suggestive of A4 not being the cause (in-and-of itself) of Alzheimer’s is that many people with no copies of A4 still get Alzheimer’s and not everyone with one or even two copies of A4 do.
2. The saying, “Genetics load the gun and environment pulls the trigger,” drives home there being more at play than genes. A4 carriers fare better relative to cognition and longevity than non-carriers in some cultures and circumstances.
3. Being A4/4 was prominent (and generally the only profile) during much of our evolution including the uptick in our longevity as a species.

As A4/4 was the prominent profile during the evolution of our species, I prefer labeling A4 (if one feels the need to do so) the Ancestral gene or allele.

Might we have tunnel vision looking in only one direction

As the prominent profile, A4/4 was advantageous during our evolution, but today A4/4 is considered to be the genetic equivalent of rolling snake eyes—a worst case roll of the dice. But, how can this be? To me, the deeming of A4/4 as being detrimental today is more of a contextual issue than it is a given as the disparity between the past and present utility of A4 speaks to more of a mismatch with modern living.

Humans evolved in environments that radically differ from those we currently experience; thus, traits that were once advantageous may now be “mismatched” and disease-causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit “genotype by environment” (GxE) interactions, with different health effects in “ancestral” versus “modern” environments. Applying an evolutionary mismatch framework to understand disease susceptibility

Taking into consideration Alzheimer’s association with modern chronic inflammatory disease, directing attention to the future–for novel interventions–as well as to the past–for time-honored implications–would be prudent.

Relatively speaking, might A4 be a bit of a scapegoat, taking the blame for what unhealthy and toxic modern living caused?

A4 risk mitigation is more likely to come from considering both the modern and the ancestral. Fueling public perception of A4, the current doomsday maligning is generating fear more than it is generating useful information. If folks knew the history and disease correlations (chronic modern disease), they would likely be more proactive.

Being an A4/4, I still live in the modern hi-tech world, but also (and as much as possible) am grounded in the traditional natural world. Something I believe to be an A4/4 perk is that I intuitively know that being outside, exposure to natural microbes, syncing with natural cycles (light, seasons), being physical, and eating nutrient dense whole food grown the way nature intended are necessities for my staying healthy and productive. I likely resonate with these inputs more than others, but argue it’s in everyone’s (A4 carrier or not) best interest to lean in this direction.

As the CoFounder of Cellementals, I formulated Cellemental Complete with my A4/4 status in mind. It is something that truly resonates with my body. I have also discovered that I not only crave it, but look forward to taking it. By replenishing nutrient dense whole food elements that were traditionally consumed, but lacking today, I support the bridging of the modern with the ancestral!

Bringing the balance your body craves

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Resources:

Applying an evolutionary mismatch framework to understand disease susceptibility

APOE4 is associated with elevated blood lipids and lower levels of innate immune biomarkers in a tropical Amerindian subsistence population

Exercise, APOE genotype, and the evolution of the human lifespan

A Quarter Century of APOE and Alzheimer’s Disease: Progress to Date and the Path Forward

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