Women get Alzheimer’s regarding twice as often as men. One does not know exactly why this is so. New research suggests it may be due to more deposits of the protein tau in the brain, promoted by an enzyme found on the female X chromosome.
The amount of tau protein in the brain is kept in balance by various enzymes. One of them is the USP11 enzyme, which leads to greater accumulation of tau protein. In animal studies, the scientists found that higher activity of the USP11 enzyme made female mice more susceptible to tau accumulation, which is typical of Alzheimer’s disease.
The gene for USP11 is on the X chromosome, one of the two sex chromosomes in every cell. Women have two, men only one. Normally, one of the two X chromosomes is “muted”. However, the USP11 gene does not appear to become completely inactive as a result. As a result, the female brain contains greater amounts of USP11, which promotes greater accumulation of tau protein.
“When a tau protein is no longer needed for the function of its nerve cell, it is usually eliminated. Sometimes this clearing process is disturbed, so that dew accumulates in nerve cells. This leads to damage to nerve cells in diseases called tauopathies. Of these, Alzheimer’s disease is the best known,” explained Prof. David Kang from Case Western Reserve University in Cleveland, who published the study with his team in the journal Cell. He was pleased with this result because the activity of enzymes can usually be specifically inhibited by certain active substances. “We hope to develop a drug that works in this way to protect women from the higher risk of Alzheimer’s,” Kang said.
Which: DOI 10.1016/j.cell.2022.09.002
