Alzheimer’s Disease: Women Are Twice More Likely To Be Affected Than Men

Alzheimer’s disease is the most common type of dementia, affecting 5.8 million North Americans in 2020. As the population ages, the incidence is expected to rise.

This means that understanding why and how Alzheimer’s develops is becoming increasingly important so that researchers can set new drug targets and doctors can intervene early.

Researchers have discovered some genetic variants that are associated with an increased risk of Alzheimer’s disease.

Research on Alzheimer’s Disease

A pair of X chromosomes are present in every female individual. All female human body cells contain just one transcriptionally active X chromosome because one of the X chromosomes will be inactivated early on in embryonic development.

Now, a recent study by scientists at Case Western Reserve University in Cleveland has suggested that one of the genes that escape X chromosome inactivation may be responsible for a female’s greater risk of developing Alzheimer’s.

In and around the brain’s nerve cells of people with Alzheimer’s disease, tangles of a protein called tau cause cell signalling to be disrupted.

Not only does Alzheimer’s have this misfolding, but so do some other neurodegenerative diseases, which causes the aggregation of these proteins. Tau is an enzyme that develops in healthy neurons but is then removed by kinases, preventing tau from routinely accumulating.

The accumulation of tau and the formation of the amyloid plaques that characterise Alzheimer’s disease, according to researchers, could be caused by systems that thwart this process.

Previous studies have demonstrated that women had higher levels of tau deposits in their brains prior to the onset of Alzheimer’s symptoms; some experts believe this may be a foundational condition for the disease.

The ubiquitin-specific peptidase 11 (USP11) protein, whose gene is produced on the X chromosome and avoids X chromosome inactivation, is thought to remove a molecule from the tau protein that increases the likelihood that it will tangle. Tau builds up as a result of this.

Broad Takeaway From The Research

Prof. Julie Williams, director of the Dementia Research Institute at Cardiff University in the United Kingdom, whose work focuses on identifying gene loci and variants that increase a person’s risk of developing Alzheimer’s disease, stated that these observations were “of great interest to the field.”

In an interview with Medical News Today, she stated:

“I would not go as far as saying it’s causing the sex difference, but it may be contributing, but there’s a bit more work that needs to be done to really stand that up. But it is a very interesting and novel finding.”

Researchers have hypothesised that the increased risk of Alzheimer’s disease is caused by both the USP11 protein’s ability to regulate estrogen-induced oestrogen receptor activity and the dysregulation of tau protein clearance that results from greater levels of the protein in females.

One drawback of the paper, according to the authors, was the absence of human replication of the data.