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Epidemiological studies have shown that women are twice as likely to develop Alzheimer's disease (AD) as men, but the cause of this phenomenon is unclear.
Now, a study led by Professor Ye Keqiang of the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences has provided a definitive answer to the mystery that has plagued humanity for decades.
The findings were published March 2 in the journal Nature.
Combined with previous research, Professor Ye's team established the theory that the C/EBPβ/AEP pathway is the core factor driving the pathogenesis of neurodegenerative diseases.
Professor Ye said: "Based on this theory, our team looked for female hormones that changed significantly during menopause and tested which hormone selectively activated the C/EBPβ/AEP pathway. ”
*Most women have natural menopause between the ages of 45 and 55.
The incidence of Alzheimer's disease is higher in older women, with cognitive decline associated with visceral obesity, energy homeostasis, and bone loss during menopause transitions. Inhibiting the effects of follicle-stimulating hormone (FSH) reduced body fat, enhanced thermogenesis, increased bone mass, and lowered serum cholesterol in mice.
Prof. Ye's team identified follicle-stimulating hormone (FSH) as the main causative factor.
During menopause, the serum concentration of FSH increases strongly, binds to homologous FSH receptors on neurons and activates the C/EBPβ/AEP pathway. This leads to lesions of Aβ and Tau, which lead to the development of AD.
The researchers used different methods to prove this finding. They used de-ovary mice and were treated with anti-FSH antibodies to block FSH and inactivate the C/EBPβ/AEP pathway. They also deleted the expression of the FSH receptor (FSHR) in neurons to eliminate the binding of FSH to FSHR in the hippocampus. Both methods alleviate pathological and cognitive impairment. In addition, knocking down C/EBPβ in AD mouse models reduces AD pathology.
In addition to studying female mice, the researchers injected FSH into male mice and found that FSH promoted AD lesions.
All of these findings suggest that increased postmenopausal FSH binds to FSHR in neurons and activates the C/EBPβ/AEP pathway, which plays an important role in triggering AD pathology.
In the near future, the team will focus on dissecting the relationship between specific risk genes such as ApoE4 and FSH, and exploring why female ApoE4 carriers are more likely to develop AD.
In addition, Prof. Ye's team is extending this theory to a variety of age-related chronic diseases such as diabetes, atherosclerosis, cancer and aging.
—— TIMEPIE ——
The main reason why women are more likely to develop Alzheimer's disease than men is follicle-stimulating hormone (FSH), and FSH levels in women rise sharply before and after menopause. Inhibition of FSH improves cognition in Alzheimer's disease mice.
The Time School will continue to pay attention to and follow up the results of the relevant experiments on effective suppression of FSH, and report to the readers for the first time.
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