Alzheimer's disease: more frequent in women, why?

13/11/2022

Of the more than 6 million Alzheimer's patients in the U.S. age 65 or older, nearly two-thirds are women. A new study may help explain the gender gap - and offer clues to new treatments for helping patients of both sexes fight back.

Scientists at Case Western Reserve University zeroed in on a gene named USP11, found on the X chromosome. People assigned female at birth have two X chromosomes, while people assigned male at birth have one X and one Y. So while all males have one copy of USP11, females have two.

Imagine you're on the sidewalk of a bustling city. Just like the residents in the buildings, our brains create waste that must be hauled away. If the waste was left on the sidewalks without removal, it would pile up, seep into roadways, disrupt life, and become toxic to the environment.

In the brain, one waste product is a protein called tau. Too little tau can damage nerve cells but too much becomes toxic and can lead to neurodegenerative diseases such as Alzheimer's.

To manage tau, your brain uses a regulatory protein called ubiquitin to "tag" or signal the body that extra tau should be removed. In the city analogy, ubiquitin is like attaching a sign to a garbage bag, telling waste management to haul the bag away.

USP11's job is to give instructions to make an enzyme that removes the ubiquitin tag to maintain balance. (You don't want to get rid of all tau protein. Justsomeof it.) But if too much of the enzyme is present, too much tau gets untagged - and not enough of it gets cleared.

The study adds to a growing body of evidence that shows women may be more vulnerable than men to higher levels of tau, possibly explaining why women are affected by the disease more often than men.

Source: Medscape