UCLA researchers identify the KDM6A gene on the X chromosome as a contributor to brain inflammation linked to Alzheimer’s disease and multiple sclerosis. Because women typically have two X chromosomes and lose estrogen at menopause — an anti‑inflammatory hormone — researchers suggest a pathway by which inflammation risk could increase. Mouse experiments showed that disabling KDM6A improved an MS‑like condition, and experts say HRT may relieve symptoms and potentially reduce inflammation, but human trials and individualized medical advice are needed.
UCLA Study Links Estrogen Loss and X‑Chromosome Gene to Brain Inflammation; HRT May Help — But Caution Advised
New research from UCLA suggests a genetic and hormonal pathway that may help explain why some inflammatory brain disorders — including Alzheimer’s disease and multiple sclerosis (MS) — are more common or more severe in women.
Key Findings
Investigators identified the KDM6A gene, located on the X chromosome, as a contributor to brain inflammation in laboratory models. Because women typically carry two X chromosomes, researchers propose women may receive a higher dose of KDM6A activity, which could increase vulnerability to inflammation-driven brain disorders. The study also ties menopause‑related estrogen loss to increased inflammation, since estrogen has anti‑inflammatory effects in the brain.
What the Study Did
In mouse experiments, UCLA researchers deactivated the KDM6A gene and observed improvement in an animal model that mimics aspects of multiple sclerosis. While these results are promising, authors note that mouse findings do not automatically translate to humans and further clinical research is needed.
Implications for Hormone Replacement Therapy (HRT)
Because estrogen is anti‑inflammatory, the study raises the possibility that hormone replacement therapy (HRT) could reduce brain inflammation associated with menopause and potentially lower long‑term risk for some neurodegenerative conditions. Clinicians and patients commonly report symptom relief on HRT — including better sleep, reduced brain fog, and fewer hot flashes — which may also indirectly reduce risk factors such as chronic sleep disruption.
“There’s some bone protection, there’s also some cardiac protection, and there may be some benefit for long‑term disorders, things like dementia,” said Dr. Shelly Holmstrom, an OBGYN with AdventHealth.
“All hormone replacement therapy is really doing is replacing something that is being removed from your body in a medically supervised fashion,” said Saad Alam, CEO and co‑founder of Hone Health.
Caveats and Next Steps
Important cautions: the core experimental result comes from animals, not clinical trials. HRT has known benefits and risks that vary by individual (age, health history, type and timing of therapy). Experts urge women to discuss symptoms, individual risk factors, and testing options with their health care providers before starting or changing HRT.
Researchers recommend additional studies to confirm whether KDM6A or estrogen modulation can be targeted safely and effectively in humans to reduce brain inflammation and disease risk.
Patient Perspective
One patient, Tracy Middleton, reported improved sleep, steadier cycles, and relief from hot flashes after starting HRT: “I’m sleeping so much better now... it’s helping with symptom relief, but then I’m also really excited about the long‑term effects of it.”
Source
This story is based on UCLA laboratory research and interviews reported by FOX 13’s Danielle Zulkosky.
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