Recent research has shed light on the reasons women are more susceptible to developing Alzheimer’s Disease, and the answer lies in sex chromosomes.

Statistics indicate that approximately 944,000 individuals in the UK are living with dementia, with about 7 million affected in the US.

Alzheimer’s Disease, the leading form of dementia and a major cause of death in Britain, impacts around 60% of those diagnosed with this debilitating condition.

According to the Alzheimer’s Society, about two-thirds of these Alzheimer’s cases are found in women.

In an effort to understand this gender disparity, researchers at UCLA Health have identified a gene that promotes inflammation in the female brain. This discovery could provide insight into why women are more frequently diagnosed with Alzheimer’s and Multiple Sclerosis.

Studying mice who had been genetically bred to have characteristics of MS, the UCLA team were able to identify a gene on the female X chromosome that drives inflammation in the immune cells in our brains called microglia. 

When they were able to ‘deactivate’ the gene, known as Kdm6a, the multiple sclerosis-like disease and neuropathology were both improved, with stronger results seen in the female mice compared to their male counterparts. 

The study, published in the journal Science Translational Medicine, concluded that because females have two X chromosomes they get a ‘double dose’ of harmful inflammation compared to males who have XY chromosomes. 

Alzheimer’s Society estimates that two thirds of Alzheimer’s Disease diagnoses are in women

The researchers also found that Metformin – a diabetes medication prescribed more than 26.4 million times in England in 2024 – could be a potential treatment after they used it to stifle the gene and its inflammatory molecules.

Study lead author Dr. Rhonda Voskuhl, director of the Multiple Sclerosis Program at UCLA Health and lead neurologist for the UCLA Comprehensive Menopause Program, said: ‘It has long been known that there are sex differences in the brain. These can impact both health and neurological diseases.

‘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.’

Dr Voskuhl said the findings may also have implications for explaining a connection to brain fog in healthy women during menopause.

Speaking of how her team’s interventions were more significant in female mice compared to male, she said it all comes down to the double chromosome. 

She said: ‘This is consistent with there being “more to block” in females due to having two copies of the X-linked gene. 

‘It’s also why females are more likely to get MS and AD than males. 

Dr Voskuhl said the findings may also have implications for explaining a connection to brain fog in healthy women during menopause (stock image)

This has implications for the clinic. Women may respond differently to metformin treatment than men.’

While there is no cure for dementia, early diagnosis allows time for personalised treatment plans to be put in place, and for doctors to prescribe drugs and treatments which can prolong the onset of the disease. 

A landmark study last year suggested almost half of all Alzheimer’s cases could be prevented by tackling 14 lifestyle factors.

Experts claimed the study, published in the prestigious journal The Lancet, provided more hope than ‘ever before’ that the memory-robbing disorder that blights the lives of millions can be prevented.

Alzheimer’s Disease is the most common form of dementia and affects 982,000 people in the UK.

Alzheimer’s Research UK analysis found 74,261 people died from dementia in 2022 compared with 69,178 a year earlier, making it the country’s biggest killer.

Sedentary lifestyles in the UK, with Brits spending their workhours deskbound, then sitting in a train or car on their way home to sit down in front of the TV, have been estimated to kill thousands each year.

One 2019 estimate put the annual death toll at 70,000 people a year with the health issues caused costing the NHS £700million each year to treat.

The WHO puts the annual global death toll from physical inactivity at around 2million per year, making it in the running to be among the top 10 leading causes of global death and disability.

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