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 signaling
NOBEASTSOFIERCE/SCIENCE PHOTO LIBRARY
The biggest known genetic risk factor for Alzheimer’s disease may boost fertility among women, a finding that could eventually help develop new fertility treatments.
Every person inherits two copies of the apolipoprotein E (APOE) gene, which comes in three variants, or alleles: APOE2, APOE3, and APOE4. These encode for slightly different forms of a protein that helps to transport fats and cholesterol – which is important for making cells, hormones, and vitamin D – around the body.
Studies have previously shown that individuals carrying an APOE4 allele have an increased risk of Alzheimer’s and heart disease, mainly focusing on people living in the US or Europe. APOE4 leads to higher cholesterol uptake from food compared to APOE3 or APOE2. Elevated cholesterol levels can lead to artery blockage and heart disease. Research has also linked excessive cholesterol in brain cells to slowed brain signaling, increasing the risk of dementia.
Despite the negative impacts of the APOE4 allele, it occurs in 15 to 25 percent of the population in Europe and the US, says Benjamin Trumble at Arizona State University. Trumble suggests that APOE4 may persist from generation to generation because Alzheimer’s and heart disease typically occur later in life when individuals tend to not reproduce.
Alternatively, APOE4 may offer some evolutionary benefits that are difficult to disentangle in Western communities with better access to modern amenities like birth control, according to Trumble.
To investigate further, Trumble and his colleagues focused on the Tsimané, an indigenous hunter-gatherer group in Bolivia who do not have access to birth control. They analyzed the genetics and fertility of 795 Tsimané girls and women aged 13 to 90 years old.
The study found that 80 percent of the participants carried two copies of APOE3, while 18.5 percent carried one copy of APOE4 and one copy of APOE3. The remaining 1.5 percent carried two copies of APOE4. None 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 an average of 0.4 more children by around 47 years old compared to those with two copies of APOE3. Women with two copies of the APOE4 allele had an average of around 1.7 more children than those with two copies of APOE3.
Furthermore, women with at least one copy of APOE4 gave birth again 10 percent sooner after their previous birth compared to those with two copies of APOE3. There was also a roughly 10-month difference in the age of giving birth to the first child, with those having at least one copy of APOE4 doing so earlier.
In an environment where food scarcity is a challenge and cholesterol levels may be lower, the increased cholesterol uptake due to APOE4 could enhance fertility, suggests Trumble. This may explain why the allele has been retained through evolution.
The findings on how APOE4 affects fertility could potentially pave the way for new fertility treatments, according to Reinaldo Barreto Oriá at the Federal University of Ceará, Brazil.
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