A new study from the Karolinska Institute has revealed a promising strategy for protecting women from neurodegenerative diseases like Alzheimer’s.
The study, led by Associate Professor Silvia Maioli, zeroes in on a specific brain protein, CYP46A1, and its role in preventing these diseases.
Published in Science Advances, the research primarily conducted on mice, demonstrates that activating CYP46A1 could be key in shielding women from Alzheimer’s. This protein plays a crucial role in managing cholesterol in the brain.
It converts excess cholesterol into a substance called 24S-hydroxycholesterol (24OH). By increasing levels of CYP46A1, the study found an increase in 24OH production, particularly beneficial for female mice.
In female mice, heightened CYP46A1 activity led to healthier neurons, better memory, and increased estrogen activity.
This was observed both in aging mice and those with menopause-like conditions. Interestingly, these positive effects weren’t noticed in male mice.
The study also looked at human data, focusing on patients with Alzheimer’s disease. It found that higher levels of 24OH in the cerebrospinal fluid correlated with lower levels of Alzheimer’s markers like tau, but this correlation was only evident in women.
This discovery is particularly significant given that two-thirds of individuals with Alzheimer’s disease are women. Additionally, early menopause is a known risk factor for cognitive decline.
Estrogen, a hormone not just produced in the ovaries but also in the brain, is vital for maintaining healthy neurons.
The activation of CYP46A1 seems to increase estrogen activity in the brains of menopausal and elderly female mice, suggesting a potential female-specific treatment avenue.
Another intriguing aspect of the study is the connection with the anti-HIV drug Efavirenz. Previous research indicates that Efavirenz can pharmacologically activate CYP46A1.
Professor Maioli suggests that this approach, targeting cholesterol metabolism through CYP46A1 activators like Efavirenz, could be a novel way to enhance estrogen-mediated neuroprotection in women at risk of Alzheimer’s disease.
This study opens up exciting possibilities for future treatments. It suggests that by focusing on cholesterol turnover and sex hormones, we might have found potential targets for therapies aimed at preventing or slowing down neurodegenerative diseases in women.
This approach could be a game-changer in the fight against conditions like Alzheimer’s, offering new hope and direction in protecting the brain health of women worldwide.
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The research findings can be found in Science Advances.
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