New Study Suggests Sex Hormones Play a Crucial Role in the Development of Alzheimer’s Disease
Approximately 32 million people worldwide suffer from Alzheimer’s disease, and of that number, about two-thirds are women. Researchers from the University of Western Ontario have recently conducted a study that reveals female sex hormones play a significant role in how Alzheimer’s disease manifests in the brain.
The study, which appears in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, sheds light on the underlying biological reasons behind the higher prevalence of Alzheimer’s disease in women.
Women are more at risk due to several factors, including longevity. Women tend to live longer than men in high-income countries by 5.2 years and in low-income countries by 3.8 years. Genetics also play a role, as a study published in October 2022 identified a gene on the X chromosome that enhances the accumulation of tau protein in the brain, a key factor in Alzheimer’s disease. Since females have two X chromosomes, they may have a higher likelihood of having higher levels of tau protein in the brain.
Additionally, research indicates that the fluctuating levels of hormones during menopause may contribute to the risk of Alzheimer’s disease. A study published in March 2022 found that the follicle-stimulating hormone (FSH), which rises during perimenopause, is linked to Alzheimer’s risk. Furthermore, research presented in 2023 found that menopausal women experiencing frequent hot flashes during sleep had a higher risk.
Dr. Vania Prado, a professor at the University of Western Ontario and senior author of the study, stated that the team decided to investigate the role of female sex hormones in Alzheimer’s disease due to the chemical changes in the brain that contribute to amyloid pathology, one of the hallmarks of the disease.
The researchers focused primarily on the female sex hormone estradiol. They observed that cholinergic neurons, which produce acetylcholine crucial for memory and cognition, can be damaged by beta-amyloid accumulation in the brain associated with Alzheimer’s disease.
By conducting tests on mice and brain scans of older humans, the researchers found that when estradiol was present, the relationship between acetylcholine and toxic amyloid was lost. However, when sex hormones were eliminated, the relationship was reconnected, potentially increasing Alzheimer’s pathology. This is particularly important as estradiol levels decrease in postmenopausal women.
While the exact mechanisms behind how estradiol affects the build-up of beta-amyloid protein in the brain remain unclear, evidence suggests that low levels of estradiol may affect how immune cells respond to amyloid in the brain and increase amyloid pathology.
Dr. Verna Porter, a neurologist and director of Dementia, Alzheimer’s Disease, and Neurocognitive Disorders at Providence Saint John’s Health Center in Santa Monica, CA, emphasized the significance of these findings for assessing Alzheimer’s risk in women. She believes that understanding the impact of sex-specific factors, such as estradiol and cholinergic signaling, can greatly influence risk assessment and management.
Moving forward, healthcare professionals may need to consider a patient’s hormonal status, including their menopausal stage and the role of estradiol when assessing their Alzheimer’s risk. Taking these factors into account can lead to a more personalized and informed approach to risk assessment and management for female patients, especially those in the perimenopausal age range.
Dr. Porter also emphasizes the importance of monitoring cognitive health, maintaining cognitive stimulation, and adopting a healthy diet to reduce the risk of Alzheimer’s disease, particularly for perimenopausal women.
This study provides valuable insights and highlights the importance of further research to better understand the role of sex hormones in Alzheimer’s disease. With a better understanding of these factors, healthcare professionals can develop more effective strategies for prevention, early detection, and treatment of this devastating disease.