Female chromosomes may protect against Alzheimer’s

26 August 2020

Researchers in the US have found that having a second X chromosome may increase resilience to Alzheimer’s disease. The findings are published today (Wednesday 26 August) in the journal Science and Translational Medicine.

Our genes are wound up into structures called chromosomes. Humans have 23 pairs of chromosomes. Twenty-two of these pairs look the same in both males and females. The 23rd pair, are the sex chromosomes. There are two types of sex chromosome, known as X and Y. Females have two X chromosomes in their cells, while males have an X and a Y chromosome in their cells.

Researchers from the University of California looked at the effect of sex chromosomes on mice with features of Alzheimer’s disease. They studied mice with different arrangements of sex chromosomes while controlling factors such as levels of sex hormones to tease out the role that chromosomes play in Alzheimer’s.

A second X chromosome increased life expectancy and decreased brain dysfunction in mice with features of Alzheimer’s. The researchers highlighted evidence of a second X chromosome providing resilience to Alzheimer’s changes through a gene called Kdm6a.

In studies of human brain tissue, they found that higher levels of Kdm6a activity were associated with slower cognitive decline.

Alzheimer’s Research UK’s expert opinion

Dr Sara Imarisio, Head of Research at Alzheimer’s Research UK, said:
“Investigating the causes of sex differences in diseases like Alzheimer’s provides important opportunities to understand how they develop and explore potential avenues for future treatments.

“More women than men develop Alzheimer’s so the suggestion that women’s genetic make-up could actually protect against the disease may seem a little contradictory. The researchers in this study point to women’s higher life expectancy being the cause of their increased risk. They suggest that while an extra X chromosome doesn’t prevent brain changes that trigger Alzheimer’s, it allows women to live with these changes for longer.

“Increased levels of a protein produced by a gene called kdm6a, which is found on the X chromosome, protected mice in this study from the effects of Alzheimer’s-like changes. Findings like this can present new directions for drug development, but they are very much a first step and it is too early to say whether an approach like this could ever benefit people with Alzheimer’s.

“These findings mostly emerge from experiments involving mice with features of Alzheimer’s, and while we can’t be sure that the same processes are at play in people with the disease, the researchers found some evidence to support their findings in studies of human brain tissue and memory and thinking test scores.

“It’s vital that researchers continue to study the diseases that cause dementia from as many angles as possible. Through research we will keep people connected to their families, their worlds and themselves for longer.”

Want to read the science?

Science and Translational Medicine: A second X chromosome contributes to resilience in a mouse model of Alzheimer’s disease