Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly, accompanied by cognitive impairment, memory imbalance and behavioral abnormalities. With the aging of the world's population, this disease has brought a heavy burden to patients, their families and society.
The World Health Organization estimates that at least 50 million people worldwide suffer from Alzheimer's disease. Epidemiological investigation also shows that, The number of women with Alzheimer's disease is twice that of men 。 Moreover, the lifetime risk of AD in women is higher than that in men, and the disease progression rate is about three times higher.
Why women are more likely to suffer from Alzheimer's disease than men ？ Many scientists have given various possible reasons for this puzzling phenomenon. For example, some people think that lack of sleep, long-term stress, etc., may be the reason for the high incidence of AD in women; It is also suggested that women with specific risk genes are at a higher risk of developing AD; Others believe that it is related to the decrease of hormone in postmenopausal women.
Today, a research paper published in the top academic journal Nature gives a new explanation. The research team led by Ye Keqiang, a researcher from the Institute of Brain Cognition and Brain Diseases, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, and Professor Ye Keqiang from Shenzhen University of Technology, Chinese Academy of Sciences (preparatory), cooperated with Professor Mone Zaidi of Mount Sinai Medical College, New York, United States, It is the first time to reveal that the increase of follicle stimulating hormone (FSH) is an important reason why women are more likely to suffer from Alzheimer's disease than men 。
Before and after menopause, the concentration of many hormones in the body has changed dramatically. Follicle stimulating hormone is one of the core hormones. This is a gonadotropin secreted by the adenohypophysis, which is found in both women and men, and promotes the production of gametes in the ovaries and testes, respectively. During the perimenopausal period, the body content of follicle stimulating hormone in women increases rapidly to more than 10 times ； In contrast, the level of FSH in elderly men of the same age group is only 2-3 times higher.
The research team found that, Rapidly increased FSH can directly act on hippocampal neurons and cortical neurons of the brain, selectively activating a signal pathway: C/EBP β/AEP 。 The previous work of the team pointed out that this molecular signal pathway is the core driving factor leading to neurodegenerative diseases such as Alzheimer's disease.
This molecular pathway activates δ - secretase AEP through transcription factor C/EBP β, promotes the cleavage of amyloid precursor protein (APP), and then Initiate A β increase and Tau protein aggregation These changes are typical pathological phenomena of Alzheimer's disease.
To verify Follicle stimulating hormone affects the production of Alzheimer's disease by affecting the C/EBP β/AEP pathway The research team conducted experiments from four different perspectives and ways through mouse models.
Researchers injected exogenous follicle stimulating hormone into Alzheimer's disease mouse model and found that both male and female mice would accelerate the formation of relevant pathological changes. contrary, In ovariectomized female AD mice to simulate menopause, blocking the effect of follicle stimulating hormone with antibodies can reduce pathological changes, and the cognitive level of mice has also been restored to a certain extent 。
Similarly, knockout of follicle stimulating hormone receptor in neurons of Alzheimer's disease model mice or knockout of C/EBP β makes the C/EBP β/AEP pathway unable to be activated, which can alleviate the pathological symptoms of mice after ovariectomy and enhance the recovery of memory.
Based on these results, the research team confirmed from multiple aspects that, Follicle stimulating hormone leads to the pathological changes related to Alzheimer's disease through the C/EBP β/AEP pathway, which further reveals the specific mechanism that the incidence of Alzheimer's disease in women is higher than in men 。
Dr. Xiong Jing, the co first author of the article, is currently the deputy chief physician of the Department of Neurology, People's Hospital of Wuhan University, engaged in the research, diagnosis and treatment of the pathogenesis of AD and Parkinson's disease (PD). She said: "During women's menstruation, estrogen increases, and inhibits the increase of follicle stimulating hormone through brain regulation, so as to cycle. With the growth of age, ovarian function declines. After menopause, female estrogen decreases, and follicle stimulating hormone is no longer inhibited, thus women are more likely to suffer from Alzheimer's disease 。”
The research team said that after the discovery of follicle stimulating hormone, an important pathogenic factor Specific risk genes such as ApoE4 Relationship with follicle stimulating hormone Conduct in-depth research at the mechanism level to explain why ApoE4 Female carriers are more likely to get sick.
Wang Jianzhi, professor of Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology commented:“ This important discovery not only provides a new cause and mechanism for women to be more vulnerable to Alzheimer's disease, but also provides a new molecular target for early clinical screening and intervention of Alzheimer's disease 。”
Professor Ye Keqiang, the corresponding author of the paper, introduced that the specific antibody against FSH is being studied in preclinical stage, with a view to realizing a new treatment strategy for Alzheimer's disease in the near future.
In the face of higher risk, how can women reduce the incidence of Alzheimer's disease ？ In this regard, Professor Ye said that balanced diet, keeping an optimistic attitude, avoiding excessive pressure, reasonable exercise, and ensuring adequate sleep time and quality can help reduce inflammation in the body, delay the onset of menopause, and to some extent, delay the onset of disease.
reference material:
[1] Jing Xiong et al。， （2022） FSH blockade improves cognition in mice with Alzheimer’s disease。 Nature。 Doi： https：//doi.org/10.1038/s41586-022-04463-0
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