November 10, 2022 – Of the more than 6 million Alzheimer’s disease patients in the United States aged 65 or older, approximately Two-thirds of women. new study It may help explain the gender gap — and provide evidence for new treatments to help patients of both sexes resist.
Scientists at Case Western Reserve University focused on a gene called USP11, found on the X chromosome. People assigned to female at birth have two X chromosomes, while people assigned to male at birth have one X and one Y. So while all males have one copy of USP11, females have two.
Your body’s garbage collection system
To understand the role of USP11 in the body, imagine that you are on the sidewalk of a bustling city. Just like building occupants, our brains create waste that must be thrown away. If waste is left on sidewalks without being removed, it will build up, seep into roads, disrupt life and become toxic to the environment.
One of the waste products is a protein called tau. Too little tau can damage neurons, explained researcher David Kang, Ph.D., and Jung A “Alexa” Wu, Ph.D., who led the study. But excessive consumption becomes toxic and can lead to neurodegenerative diseases such as Alzheimer’s disease. (In fact, new search It suggests that testing for changes in tau may one day help doctors diagnose Alzheimer’s disease early.)
To manage tau, your brain uses a regulatory protein called ubiquitin To “mark” or signal to the body that extra tau should be removed. In the city analogy, ubiquitin is like attaching a tag to a garbage bag, telling the waste department to pull the bag away.
The job of USP11 is to instruct the making of an enzyme that removes the ubiquitin tag to maintain homeostasis. (You don’t want to get rid of all your tau protein. JustsomeBut if there is too much enzyme, too much tau is not marked – and not enough is removed.
“Our study showed that the level of USP11 is higher in females than in males in both humans and mice,” says Kang. “This is already true before the onset of dementia. But once someone has Alzheimer’s disease, the USP11 standard is much higher – regardless of gender.”
The study adds to a A growing body of evidence It shows that women may be more susceptible than men to higher levels of tau, and may explain why women get sick more often than men.
But what if there was a way to “turn off” or deactivate the USP11 gene? Could this help prevent Alzheimer’s disease? Can this be done safely?
What happened when the gene was eliminated?
To examine these questions, the researchers used a genetic manipulation method to completely delete the USP11 gene in mice. Then they checked the mice for changes. Results? The mice looked fine.
“Mice are bred well,” says Wu.
It would not be possible – or ethical – to remove the gene from humans. But when a medical condition renders a particular gene unhelpful, that gene can be partially blocked or gene expression can be reduced with medications. In fact, drugs that target enzymes are common. Examples include statins for cardiovascular disease or HIV treatments that inhibit protease enzymes.
“If we were able to identify a type of drug that would block USP11, our study suggests that it is well tolerated and benefits women,” Wu says.
Kang also warns that the process of creating such a treatment takes at least 10 to 15 years. The researchers say they’d like to shorten the timeline and plan to study the drugs currently approved by the FDA to see if any might work to target USP11 gene activity — and hopefully, offer a new treatment for Alzheimer’s disease sooner.