New Study Finds Brain Protein Could Protect Women from Alzheimer’s Disease
A new study published in Sciences Advances has identified a brain protein that could potentially protect women from developing neurodegenerative diseases such as Alzheimer’s. The study, led by Silvia Maioli, associate professor at the Department of Neurobiology at the Karolinska Insitutet in Stockholm, focused on the protective effects of the CYP46A1 protein in mice and humans.
The role of estrogen on cognitive decline is well established, and the study found that menopause and the subsequent drop in estrogen levels could be a risk factor for dementia, particularly in women as dementia affects 70% of cases. Estrogen is known to play a crucial role in maintaining brain health and memory learning ability, but its decline during menopause can lead to cognitive deterioration and an increased risk of Alzheimer’s. Additional studies have shown that early menopause can triple the rate of cognitive decline in women.
One hypothesis for why men are less affected by dementia is that the enzymatic system responsible for converting androgen hormones into estrogens is present in the brains of men, providing them with a protective advantage in old age.
While consistent exercise and a healthy diet have been shown to reduce the risk of dementia in both men and women, hormone replacement therapy (HRT) has also been associated with a reduced risk of Alzheimer’s and dementia. However, the study focused on the CYP46A1 protein as a potential therapeutic approach to protect women from developing Alzheimer’s disease.
The CYP46A1 protein plays a vital role in the brain by eliminating excess cholesterol and transforming it into a product called 24S-hydroxycholesterol (24SOH). The study found that increased levels of CYP46A1 in the brains of female mice led to healthier neurons, higher estrogenic activity, and improved memory and learning abilities. However, male mice showed worsening memory and the accumulation of a male hormone, which blocked the protective effects of 24SOH.
Subsequent human studies validated these findings and suggested that the activation of CYP46A1 and higher levels of 24SOH could have a protective effect against Alzheimer’s disease exclusively for females.
The study also revealed that low doses of the HIV drug Efavirenz can activate CYP46A1, potentially offering a new therapeutic approach to promote estrogen-mediated brain protection in women at risk of Alzheimer’s disease, such as those with early menopause.
These findings have the potential to open up new preventive therapies against neurodegenerative diseases and provide hope for women at risk of developing Alzheimer’s.