Previous research finds that women are twice as likely as men to develop Alzheimer’s disease (AD), but the cause of this phenomenon has been unclear.
In a new study from the Chinese Academy of Sciences, researchers provide a clear answer to this mystery that has puzzled mankind for decades.
Integrating their previous studies, the team has established the theory that the C/EBPβ/AEP pathway is the core factor driving the pathogenesis of neurodegenerative diseases.
Based on this theory, the team searched for female hormones that are dramatically changed during menopause and tested which hormone selectively activates the C/EBPβ/AEP pathway
They found the follicle-stimulating hormone (FSH) is the major pathogenic factor.
During menopause, the serum concentration of FSH strongly increases, binding to the cognate FSH receptor on neurons and activating the C/EBPβ/AEP pathway.
This results in Aβ and Tau pathologies, leading to the development of AD.
The researchers employed different methods to demonstrate this finding.
Using ovariectomized mice, they used anti-FSH antibody treatment to block FSH and inactivate the C/EBPβ/AEP pathway.
They also deleted FSH receptor (FSHR) expression in neurons to abolish the binding of FSH to FSHR in the hippocampus.
Both of these methods alleviated pathology and cognitive dysfunction. In addition, knockdown of C/EBPβ in the AD mice model decreased AD pathologies.
The researchers also injected FSH into male mice and discovered that FSH promoted AD pathologies.
All these findings suggest that increased FSH after menopause binds to FSHR in neurons and activates the C/EBPβ/AEP pathway, which plays an important role in triggering AD pathology.
The findings demonstrate that the C/EBPβ/AEP signaling pathway acts as a core factor in these age-dependent diseases, which may help disclose how a variety of risk factors mediate neurodegenerative diseases
The team is extending this theory to numerous age-dependent chronic diseases such as diabetes, atherosclerosis, cancer, and aging.
If you care about Alzheimer’s disease, please read studies about a primary cause of Alzheimer’s disease and findings of the critical time window to halt Alzheimer’s disease.
For more information about Alzheimer’s disease treatment and prevention, please see recent studies about a major breakthrough in Alzheimer’s disease treatment and results showing that many dementia cases can be prevented by avoiding these 12 things.
The study is published in Nature and was conducted by Prof. Keqiang Ye et al.
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