Gene variant that raises Alzheimer’s risk may boost fertility in women

The genetic variant APOE4 substantially raises the risk of Alzheimer’s disease, but it has also been linked to women having more children in an Indigenous group in Bolivia

By Carissa Wong

9 August 2023

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

The biggest known genetic risk factor for Alzheimer’s disease may boost fertility among women, a finding that could eventually help to develop new fertility treatments.

Every person inherits two copies of the apolipoprotein E 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 people carrying an APOE4 allele have an increased risk of Alzheimer’s and heart disease, but these mainly focused on people living in the US or Europe. APOE4 increases the uptake of cholesterol from food compared with APOE3 or APOE2. Too high cholesterol levels can clog arteries, leading to heart disease. Research has also linked too much cholesterol in brain cells to slowed brain signalling, which may increase the risk of dementia.

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“Despite the fact the allele has these negative impacts, it still occurs in between 15 to 25 per cent of the population across Europe and the US,” says Benjamin Trumble at Arizona State University. APOE4 may pass from generation to generation despite its negative effects because Alzheimer’s and heart disease generally occur later in life, when people tend to not reproduce, he says.

Alternatively, APOE4 may have benefits that have caused it to be retained as humans evolved, says Trumble. These benefits may be difficult to untangle in Western communities that have better access to modern amenities, such as birth control, he says.

Trumble and his colleagues therefore focused on the Tsimané, an Indigenous hunter-gatherer group in Bolivia. They analysed the genetics and fertility of 795 Tsimané girls and women, aged 13 to 90 years old, who lack access to birth control. No transgender people were included in the study. Fertility was assessed according to when the participants had children, how many they had and the time between them.