Why women are more at risk

All human females have a pair of X chromosomes. Early in embryonic development, her one X chromosome is inactivated and all cells in the female human body have only one her X chromosome that is transcriptionally active.

This helps prevent overexpression of genes present on both X chromosomes. Several genes escape this X-chromosome inactivation, but the reasons and effects are not fully understood. review outlined.

A recent study by researchers at Case Western Reserve University in Cleveland now shows that one of the genes that bypasses X-chromosome inactivation may contribute to an increased risk of developing Alzheimer’s disease in women. is proposed.appear in cell.

People with Alzheimer’s disease have protein tangles. yes Disrupts cell signaling in and around nerve cells in the brain.

Misfolding that causes aggregation of these proteins is found not only in Alzheimer’s disease, but also in other neurodegenerative diseases. Tau is formed in healthy neurons, but is removed by the action of an enzyme called tau. kinasewill not build successfully.

Researchers believe that mechanisms that disrupt this process may lead to the accumulation of tau and the development of amyloid plaques that are hallmarks of Alzheimer’s disease.

Previous research Women show more tau deposited in their brains before they develop Alzheimer’s symptoms, and some experts say this could be a fundamental event in Alzheimer’s disease. I think

Researchers ubiquitin-specific peptidase 11 The (USP11) protein, whose gene is expressed on the X chromosome, evades X-chromosome inactivation and removes molecules from the tau protein, making it easier to tangle. This leads to tau accumulation.

To test this hypothesis, they first HeLa cells — named after Henrietta Luxthe female from which the first set of cells was derived – they knocked out the USP11 and USP13 proteins.

Other experiments will examine brain tissue from deceased Alzheimer’s patients and brain tissue from patients who did not have dementia to determine whether USP11 production is deregulated in humans with Alzheimer’s disease. was included.

They found that the amount of USP11 protein was 9.5 times higher in the brain tissue of people with Alzheimer’s disease than in people without dementia.

Finally, the researchers generated mice whose genomes had the gene encoding USP11 knocked out and found that these female mice had less tau in their brains.

These observations were “very interesting for the field.” Professor Julie Williams,director Dementia Research Institute At Cardiff University in the UK, we are working to find loci and variants that increase the likelihood of developing Alzheimer’s disease.

she said medical news today In an interview:

“I wouldn’t go so far as to say that it causes a sex difference, but it could be a contributing factor, but we need to do a little more work to really prove it. But this is very interesting. is a novel discovery.”

She also notes that many of the previous genome-wide association studies done to determine which genetic variants may increase the risk of developing Alzheimer’s disease have not looked at the USP11 gene. That’s research that needs to be done,” he said.

The researchers found that the increased risk of Alzheimer’s disease is not only due to deregulation of tau protein clearance as a result of higher USP11 protein levels in women, but also because USP11 protein is estrogen– Induced estrogen receptor activity.

The lack of reproducibility of results in humans was a limitation of the paper noted by the authors.

Dr. Bert de Struper,director British Dementia Research Institute at University College London, MNT that “[i]t is the evidence [is] Although collected primarily in preclinical settings, in models of disease such as cell culture and mouse models, the experiments are sound and indeed support the paper’s overall conclusions.

“I agree with the conclusions of this paper,” he commented. Frontotemporal. “