Researchers at Arizona State University, publishing new findings in the journal Sciences Advances, have found that an Alzheimer’s disease (AD) genetic risk marker may have fertility benefits in women. The Apolipoprotein-ε4 (APOE-ε4) allele has been well studied and implicated in numerous studies for increased risk for a variety of diseases in aging populations, notably AD and cardiovascular disease. The Arizona State researchers made their discovery while searching for answers as to why this negative allele is surviving natural selection and remains prevalent in roughly 20% of the human population.
For their study, Benjamin Trumble, PhD, associate professor of evolutionary anthropology at Arizona State University’s School of Human Evolution and Social Change and lead author of the study, and colleagues Hillard Kaplan, Michael Gurven, and Jonathan Stieglitz, traveled to the Bolivian Amazon lowlands where they have been collecting demographic and biomedical for more than 20 years from the Tsimane people. A hunter-gatherer society, the Tsimae comprise more than 17,000 people spread across 90 villages and live a lifestyle that is similar to human life prior to the Industrial Revolution. This offers Trumble and his team a look into health and aging without modern influences to understand what human health was like prior to industrialization.
“For 99% of human history, we were hunter-gatherers,” Trumble said. “The world we’re living in today is really weird. It’s this built environment that we’ve created that’s entirely different from what it was throughout most of human evolution. We are now essentially operating outside of the manufacturer’s recommended warranty.”
For the new study, the investigators collected genetic data from 795 Tsiman women, aged 13 to 90, as well as information about their fertility, which included age of first birth, how long between births, total number of live births, and more.
Using these data, the team determined that women possessing the APOE-ε4 allele had 0.5 more births than those women without the allele. When two copies of the APOE-ε4 allele were present the increase jumped to two more birth compared with women without it.
“What we found in this population was that women began reproducing almost a year earlier if they had the APOE-ε4 allele and they had shorter interbirth intervals,” Trumble said.
This simple fact that having one or two copies of the APOE-ε4 allele increased fertility and number of children helps explain why, despite its negative consequences later in life, allows the allele to be unaffected by natural selection. In short, the benefits it incurs earlier in life during child-bearing years promote its presence and are not affected by its detrimental effects later in life.
“Genes that are associated with diseases that occur after the age of reproduction, or after reproduction has already started, are in a ‘selection’s shadow.’ There have been a lot of arguments about the APOE-ε4 allele, that it may be an example of selection’s shadow, that you don’t develop Alzheimer’s until after you’ve already had all your kids,” Trumble noted.
Even with the benefits of the APOE-ε4 allele that have been discovered, there remains the negative health effect of increased risk of AD and cardiovascular disease in the later stages of life.
However, this negative effect of the allele is mostly seen in Westernized nations. Trumble’s prior research has shown that the Tsimane have the lowest rates of dementia and Alzheimer’s in the world—despite having the same 20% prevalence of the APOE-ε4 allele in their population.
But a pressing question remains as to how this information can be used to improve human health across populations.
“We need to better understand global variation, and in particular, we need to kind of think outside the box and move beyond our focus on ‘this allele causes X disease’ and that’s just how it is,” Trumble concluded. “Instead, we need to take a step back and say, what about in different environments? What about in the environments in which humans evolved? Because that actually opens up a whole other possibility for prevention or treatment by being able to mimic some of the aspects of that lifestyle. If we aren’t seeing the same associations between APOE-ε4 and some outcome, then maybe if we kind of take a step back and we say, okay, what are the differences?”
