BEIJING — Prior research suggests women are twice as likely as men to develop Alzheimer’s. However, the exact cause of this gender disparity remained a mystery. Now, new research from the Chinese Academy of Sciences Headquarters finally provides a possible answer. In a nutshell, it appears to boil down to menopause.
The team centered the work on the theory that the C/EBPβ/AEP pathway is the core factor driving the development of neurodegenerative diseases like dementia and Alzheimer’s.
“Based on this theory, our team searched for female hormones that are dramatically changed during menopause and tested which hormone selectively activates the C/EBPβ/AEP pathway,” explains Prof. Keqiang Ye from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences.
FSH increases during menopause and is linked to the development of Alzheimer’s
Professor Ye and his team identified the follicle-stimulating hormone (FSH) as the major pathogenic factor linked to Alzheimer’s.
“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,” says co-corresponding study author Dr. Zaidi Mone, a tenured professor at the Mount Sinai School of Medicine in New York, in a press release.
First, they gave a group of ovariectomized mice anti-FSH antibody treatments to block FSH and inactivate their C/EBPβ/AEP pathways. Researchers also deleted FSH receptor (FSHR) expression within neurons to abolish the binding of FSH to FSHR within the mice’s hippocampus — a brain area involved in cognition and memory.
Both strategies successfully eased any cognitive issues in mice. Knocking down the C/EBPβ in the Alzheimer’s mice model also decreased any signs of Alzheimer’s on the brain. FSH was linked to the development of Alzheimer’s, as male mice injected with FSH showed more evidence of Alzheimer’s pathologies.
Overall, this work strongly shows increased FSH during menopause binds to FSHR in neurons and activates the C/EBPβ/AEP pathway. This process is vital to “triggering” Alzheimer’s onset.
“Our 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 via activating this pathway,” concludes Dr. Seong Su Kang from Emory University.
The study is available to read in Nature.