In a recent investigation, scientists at the University of Western Ontario have unveiled the substantial influence of female sex hormones on the presentation of Alzheimer’s disease in the brain. The study has been published in the Journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
This article explores the complex connection between sex hormones and the advancement of Alzheimer’s disease within the brain.
Introduction
Alzheimer’s disease is a complex and devastating neurodegenerative disorder that affects millions of individuals worldwide. While Alzheimer’s primarily affects memory and cognitive functions, it is increasingly recognized that there are gender disparities in the prevalence and progression of the disease. This has led researchers to explore the role of sex hormones, such as estrogen and testosterone, in Alzheimer’s disease.
While researchers have proposed some theories regarding the higher likelihood of Alzheimer’s disease in women compared to men, the fundamental biological causes remain elusive.
Why do women have a greater susceptibility to developing Alzheimer’s disease?
Several factors contribute to this phenomenon:
1. Longevity
One primary factor is the difference in lifespan. Women typically live longer than men. In high-income countries, women tend to outlive men by 5.2 years, and this gap is 3.8 years in low-income countries.
2. Genetics
Recent research conducted in October 2022 identified a specific gene on the X chromosome, which enhances the accumulation of Tau protein in the brain. Since females possess two X chromosomes, they may be more inclined to have higher levels of Tau protein in the brain. Tau protein accumulation is considered one of the primary factors contributing to Alzheimer’s disease.
3. Hormonal Influence
Hormones also play a role in the differing susceptibility of women to Alzheimer’s disease. A study in mice published in March 2022 revealed a connection between follicle-stimulating hormone (FSH) levels, which increase during perimenopause, and the risk of Alzheimer’s.
4. Menopausal Symptoms
Research in 2023 found that menopausal women who experience frequent hot flashes during sleep have a higher risk of developing Alzheimer’s disease.
These multiple factors collectively contribute to the increased likelihood of Alzheimer’s disease in women compared to men.
Understanding the Influence of Female Sex Hormones on Alzheimer’s Progression
Dr. Vania Prado, a professor in the Departments of Physiology, Pharmacology, Anatomy, and Cell Biology at Schulich School of Medicine & Dentistry and a researcher at the Robarts Research Institute at the University of Western Ontario, serves as the senior author of this study.
The decision to investigate the potential impact of female sex hormones on Alzheimer’s disease development was motivated by the chemical alterations within the brain that can influence and contribute to amyloid pathology, a key characteristic of Alzheimer’s disease.
Dr. Prado clarified, “One of the significant factors in regulating early pathology is the action of brain cells that release acetylcholine. Compelling evidence suggests that these brain cells can function differently and are responsive to sex hormones, including estradiol. We were aware of this from the outset.”
Upon examining the relationship between acetylcholine and Alzheimer’s pathology, the research revealed contrasting responses in male and female mice. Nevertheless, men and women affected by Alzheimer’s displayed a similar pattern. This led to the question of why these distinctions existed between mice and humans. Sex hormones, potentially due to the age of the mice typically used in research, emerged as the primary suspect.
Could Estradiol Influence the Accumulation of Harmful Amyloid in the Brain?
In this investigation, Dr. Prado and her research team centered their attention on estradiol, a female sex hormone critical for maintaining the reproductive system in women and playing a pivotal role in egg maturation and release during the menstrual cycle.
The research posits that cholinergic neurons responsible for producing acetylcholine, a crucial element for normal memory and cognitive function, are susceptible to brain damage caused by beta-amyloid accumulation, a phenomenon associated with Alzheimer’s disease.
Through a series of tests and image analyses conducted on a mouse model featuring both male and female mice and by scrutinizing brain scans of older humans, the investigators observed that estradiol disrupted the correlation between acetylcholine and toxic amyloid. However, in the absence of sex hormones, this connection was re-established, potentially leading to an escalation in Alzheimer’s pathology. This finding is particularly noteworthy since estradiol levels typically decline in postmenopausal women.
In the end, Dr. Prado concluded, “ We were quite surprised by observing the contrasting reactions in female mice, which differed from both male mice and humans, irrespective of gender. This divergence is likely attributable to the influence of female hormones, presumably reduced in women with Alzheimer’s.”
Exploring Sex-Specific Factors in Alzheimer’s Disease
Dr. Verna Porter, a distinguished neurologist and the director of Dementia, Alzheimer’s Disease, and Neurocognitive Disorders at Providence Saint John’s Health Center in Santa Monica, CA, shared her thoughts on this research.
As a physician who cares for female patients facing a heightened risk of Alzheimer’s disease, she expressed her profound interest in this study.
“The study’s revelations offer invaluable insights into sex-specific factors, particularly the influence of estradiol and cholinergic signaling in Alzheimer’s disease. Comprehending these elements can significantly shape my approach to evaluating risks and conducting discussions with female patients, especially those within the perimenopausal age bracket. In future dialogues with my female patients, I plan to incorporate these findings to provide a more personalized and informative approach to assessing and managing Alzheimer’s risk.”
Dr. Porter said these findings may also lead to a need to emphasize the importance of considering the patient’s hormonal status, including their menopausal stage and the role of estradiol, when assessing their Alzheimer’s risk.
“This would be particularly relevant for perimenopausal women, as the study suggests that estradiol may impact the relationship between cholinergic signaling and amyloid pathology,” she added.
“For those in the perimenopausal age range, we should continue to push the importance of monitoring cognitive health and considering lifestyle modifications, such as maintaining cognitive stimulation and a healthy diet, which have been associated with a reduced risk of Alzheimer’s disease,” Dr. Porter said.
Reference
- Sex hormones may play a key role in how Alzheimer’s disease develops in the brain. [Accessed October 20, 2023]. Available at: https://www.medicalnewstoday.com/articles/alzheimers-disease-linked-to-female-sex-hormones-study
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