US researchers have identified a gene on the X chromosome that drives inflammation in the female brain and explains the reason why women are disproportionately affected by conditions such as Alzheimer's disease and multiple sclerosis
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US researchers have identified a gene on the X chromosome that drives inflammation in the female brain and explains the reason why women are disproportionately affected by conditions such as Alzheimer's disease and multiple sclerosis.
The team from the University of California-Los Angeles noted that, as females have two X chromosomes, as opposed to only one in males, they get a "double dose" of inflammation, which plays a major role in ageing, Alzheimer's disease, and multiple sclerosis.
Using a mouse model of multiple sclerosis, they found the gene Kdm6a, which causes inflammation in microglia -- immune cells in the brain.
When Kdm6a and its associated protein were deactivated, the multiple sclerosis-like disease and neuropathology were both ameliorated with high significance in female mice, revealed the study, published in the journal Science Translational Medicine.
"Multiple sclerosis and Alzheimer's disease each affect women more often than men, about two to three times as often. Also, two-thirds of healthy women have 'brain fog' during menopause. These new findings explain why and point to a new treatment to target this," said lead author Dr. Rhonda Voskuhl, director of the Multiple Sclerosis Programme at UCLA Health.
When the team genetically "knocked out" the gene Kdm6a in brain immune cells, the inflammatory molecules shifted from being activated to a resting state.
The team also performed a pharmacologic "knock down" of the protein made by this gene using metformin -- widely used as a treatment for diabetes.
While these interventions were highly significant in female mice, their effect was almost undetectable in males, Voskuhl said.
"This is consistent with there being 'more to block' in females due to having two copies of the X-linked gene," said Voskuhl.
"It's also why females are more likely to get multiple sclerosis and Alzheimer's disease than males. This has implications for the clinic. Women may respond differently to metformin treatment than men."
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