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Women with a Gene Variant Linked to Increased Alzheimer’s Risk May Have Improved Fertility

Amyloid plaques in the brain of someone with Alzheimer’s disease. The condition has also been linked to too much cholesterol in brain cells, slowing brain signalling

NOBEASTSOFIERCE/SCIENCE PHOTO LIBRARY

Women with a certain gene variant linked to an increased risk of Alzheimer’s disease may actually have improved fertility, according to a recent study. This discovery could have implications for the development of new fertility treatments in the future.

Every individual inherits two copies of the apolipoprotein E (APOE) gene, which comes in three variants: APOE2, APOE3, and APOE4. These variants encode for slightly different forms of a protein that helps transport fats and cholesterol throughout the body. Cholesterol plays a crucial role in cell production, hormone regulation, and the synthesis of vitamin D.

Prior research has shown that individuals carrying the APOE4 allele have a higher risk of developing Alzheimer’s disease and heart disease. However, most of these studies have focused on populations in the US and Europe. APOE4 is associated with increased cholesterol absorption from food compared to APOE3 or APOE2. High cholesterol levels can lead to the clogging of arteries, increasing the risk of heart disease. Additionally, excessive cholesterol in brain cells has been linked to impaired brain signaling, potentially increasing the risk of dementia.

The APOE4 allele, despite its negative effects, remains present in 15 to 25 percent of the population in Europe and the US. Benjamin Trumble from Arizona State University suggests that this allele may persist across generations because Alzheimer’s and heart disease typically occur later in life when reproduction is less likely.

Alternatively, APOE4 may have provided evolutionary benefits that are difficult to decipher in Western communities with access to modern amenities such as birth control, according to Trumble.

To investigate further, Trumble and his team studied the Tsimané, an indigenous hunter-gatherer group in Bolivia. They analyzed the genetics and fertility of 795 Tsimané girls and women, ranging in age from 13 to 90 years old, who did not have access to birth control. The researchers assessed fertility based on factors such as the number of children participants had, the timing between births, and when they started having children.

The study revealed that 80 percent of the girls and women carried two copies of the APOE3 variant, while 18.5 percent had one copy of APOE4 and one copy of APOE3. Only 1.5 percent carried two copies of APOE4. None of the participants had any copies of APOE2.

Through surveys conducted between 2002 and 2022, the researchers discovered that women with one copy of the APOE4 allele and one copy of APOE3 had, on average, 0.4 more children by the age of approximately 47 compared to individuals with two copies of APOE3. Women with two copies of the APOE4 allele had around 1.7 more children, on average, compared to those with two copies of APOE3.

Additionally, participants with at least one copy of APOE4 gave birth approximately 10 percent sooner after their previous birth compared to individuals with two copies of APOE3. There was also a roughly 10-month difference in the timing of first childbirth, with those carrying at least one copy of APOE4 giving birth earlier.

In environments where obtaining enough food can be challenging and cholesterol levels may be lower, the increased cholesterol uptake associated with APOE4 could potentially enhance fertility, Trumble suggests. This could explain why the allele has been retained through evolution.

The findings of this study, which shed light on the impact of APOE4 on fertility, have the potential to pave the way for the development of new fertility treatments in the future, according to Reinaldo Barreto Oriá from the Federal University of Ceará, Brazil.

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