Women’s brains face a higher risk of Alzheimer’s and multiple sclerosis and researchers have discovered one gene could be to blame.
It is estimated that 982,000 people are living with dementia in the UK, but women over 60 are twice as likely to develop Alzheimer’s – the most common form of dementia, according to Alzheimer’s research.
Similarly, more than 7,100 people are diagnosed with multiple sclerosis (MS) each year in the UK but 71 per cent are women – meaning women are two and a half times more likely to be diagnosed with MS than men, according to MS Society.
However, researchers at UCLA in California have identified a sex chromosome and a gene that drives inflammation in the female brain – giving an insight into why women could be disproportionately affected.
“It has long been known that there are sex differences in the brain. These can impact both health and neurological diseases,” said study lead author Dr Rhonda Voskuhl, director of the Multiple Sclerosis Program at UCLA Health.
“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,” she added.
The study, published in the journal Science Translational Medicine, looked at female mice and used a mouse model of MS. Researchers identified a gene on the X chromosome that drives inflammation in brain immune cells, known as microglia.
Because 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 aging, Alzheimer’s disease and multiple sclerosis, study authors explain.
Inflammation is a natural response to damage or infection, but it too can cause damage to the body if it lasts for a long time.
When the gene, known as Kdm6a, and its associated protein were deactivated, the MS-like disease improved.
The gene was “genetically knocked out” in brain immune cells by researchers which caused the inflammatory molecules to go into a resting state.
The team also used the drug metformin – which is used as a treatment for diabetes but is currently being researched for potential anti-aging properties. It was used to “knock out” the protein made by this gene.
While these interventions were significant in female mice, their effect was almost undetectable in males, researchers said.
“This is consistent with there being ‘more to block’ in females due to having two copies of the X-linked gene,” said Dr Voskuhl, who is also a professor of neurology at UCLA Health.
“It’s also why females are more likely to get MS and Alzheimer’s than males. This has implications for the clinic. Women may respond differently to metformin treatment than men.”
She added the findings may also have implications for explaining a connection to brain fog in healthy women during menopause.
Researchers suggest a lack of oestrogen could have inflammatory effects.
“Sex chromosomes and sex hormones achieve a balance through evolution,” Dr Voskuhl said.
“There is a selection bias to do so. Females have a balance between X chromosome-driven inflammation that can be good to fight infections at child-bearing ages. This is held in check by oestrogen, which is anti-inflammatory and neuroprotective,” she added.
“As women age, menopause causes loss of oestrogen, unleashing the pro-inflammatory and neurodegenerative effects of this X chromosome, the brain immune cell.”
She explained that together, these findings may support use of oestrogens that target the brain to keep the balance, and thereby protect the brain, during menopause.
