Why Are Women More Prone to Alzheimer’s Than Men? Study Provides Hint

Nearly two-thirds of the more than 6 million Alzheimer’s patients in the U.S. who are 65 or older are female. A recent study may offer insight into potential new medicines that could aid patients of both sexes in overcoming the gender gap.

Researchers at Case Western Reserve University focused on the X chromosome’s USP11 gene. People who are born as females have two X chromosomes, whereas those who are born as males have one X and one Y. As a result, females have two copies of USP11 while all males have one.

Your body’s waste disposal system

Imagine yourself on the sidewalk of a busy metropolis in order to comprehend the function of USP11 in the body. Our brains produce trash, much like the occupants of the buildings, that needs to be removed. If the trash wasn’t picked up, it would accumulate on the sidewalks, seep into the streets, disturb daily life, and contaminate the environment.

Tau protein is one of the waste products found in the brain. According to study authors David Kang, PhD, and JungA “Alexa” Woo, PhD, too little tau can harm nerve cells. However, too much can be harmful and cause neurodegenerative conditions like Alzheimer’s. (Actually, recent research indicates that looking for changes in tau could one day assist medical professionals in diagnosing Alzheimer’s earlier.)

Your brain “tags” or tells the body to get rid of superfluous tau using a regulatory protein called ubiquitin to control tau. According to the city metaphor, ubiquitin acts as a sign instructing waste management to pick up the garbage bag.

To keep things in balance, USP11 is responsible for providing instructions for creating an enzyme that removes the ubiquitin tag. However, if there is an excessive amount of the enzyme present, too much tau gets untagged and not enough of it is cleared (you only want to get rid of some of the tau protein).

According to Kang’s research, USP11 levels are higher in females than males in both mice and humans. “That was true even before dementia started. However, regardless of gender, USP11 is substantially higher after someone has Alzheimer’s disease.

The finding adds to a growing body of research suggesting that women may be more susceptible than men to greater amounts of tau, which could account for why women are impacted by the disease more frequently than men.

But what if the USP11 gene could be “turned off” or deactivated? Could doing that help fend off Alzheimer’s? And could it be done without risk?

What Took Place After the Gene Was Removed?

The USP11 gene was entirely deleted from mice using a gene-editing technique to investigate these issues. They next looked for modifications in the mice. The outcome? The mice appeared healthy.

The mice reproduced well. Their brains appeared healthy, claims Woo.

Removing a gene from a human would not be possible or moral. However, a gene can be partially silenced or its expression can be decreased with medication if a medical condition makes it useless. In actuality, drugs that target enzymes are widely used. Examples include HIV medications that block protease enzymes or statins for cardiovascular disease.

Our findings implies that any medication that inhibits USP11 will be well tolerated and advantageous to women, according to Woo.

Kang warns that it will take at least 10 to 15 years to develop such a therapy. The researchers hope to accelerate the development of a new Alzheimer’s treatment by studying FDA-approved drugs currently on the market to see if any can target the USP11 gene activity.

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