Gene on X chromosome may explain women's higher risk of MS and Alzheimer's

A gene located on the X chromosome could explain why women have a higher risk of developing multiple sclerosis (MS) and Alzheimer's disease.

Using a mouse model of MS, scientists at the University of California, Los Angeles (UCLA) have discovered that the KDM6A gene found on the X chromosome causes inflammation in the brain. As women have two X chromosomes, one of the chromosomes in each female cell is silenced to prevent overproduction of X-linked gene proteins. However, the KDM6A gene escapes this inactivation, resulting in double the amount of the KDM6A protein produced in females compared to males, who only have one X chromosome.

'It has long been known that there are sex differences in the brain. These can impact both health and neurological diseases. MS and Alzheimer's disease each affect women more often than men, about two to three times as often,' explained Dr Rhonda Voskuhl, professor of neurology at UCLA and senior author of the study published in Science Translational Medicine.

When the KDM6A gene was deactivated in the mouse model, researchers found that the level of brain inflammation in female mice, but not in male mice, was reduced.

Furthermore, the researchers found that metformin, a drug commonly used to treat diabetes binds to the KDM6A protein and blocks its activity. When the mice were treated with metformin, symptoms of MS improved in the female mice, but there was no significant effect in the male mice.

'This is consistent with there being "more to block" in females due to having two copies of the X-linked gene,' said Dr Voskuhl. '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.'

Inflammation is known to play a major role in MS and Alzheimer's disease. MS is a chronic autoimmune disease where the immune system attacks and damages myelin, a fatty substance that surrounds and protects nerves in the brain and spinal cord, leading to inflammation and nerve damage. When myelin is damaged, the brain cannot transmit electrical signals to the rest of the body, resulting in muscle weakness and loss of sensation or coordination. Alzheimer's disease is a progressive neurodegenerative disorder leading to the gradual loss of brain cells and the connections between them.

Inflammation is also known to play a major role in ageing, with Dr Voskuhl suggesting that the findings of this study may also have implications for treating symptoms of the menopause.

'As women age, menopause causes loss of oestrogen, unleashing ... pro-inflammatory and neurodegenerative effects.'

These findings may point to new treatment approaches for MS, Alzheimer's disease and symptoms of the menopause.