FSH blockade improves cognition in mice with Alzheimer’s disease
Open accessAbstract
Alzheimer's disease has a higher incidence in older women, with a spike in cognitive decline that tracks with visceral adiposity, dysregulated energy homeostasis and bone loss during the menopausal transition 1,2. Inhibiting the action of follicle-stimulating hormone (FSH) reduces body fat, enhances thermogenesis, increases bone mass and lowers serum cholesterol in mice 3-7. Here we show that FSH acts directly on hippocampal and cortical neurons to accelerate amyloid-β and Tau deposition and impair cognition in mice displaying features of Alzheimer's disease. Blocking FSH action in these mice abrogates the Alzheimer's disease-like phenotype by inhibiting the neuronal C/EBPβ-δ-secretase pathway. These data not only suggest a causal role for rising serum FSH levels in the exaggerated Alzheimer's disease pathophysiology during menopause, but also reveal an opportunity for treating Alzheimer's disease, obesity, osteoporosis and dyslipidaemia with a single FSH-blocking agent.
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Elevated levels of follicle-stimulating hormone directly promote the accumulation of amyloid-β and hyperphosphorylated tau in the hippocampus via the C/EBPβ-δ secretase pathway, leading to neuronal apoptosis, synaptic damage and spatial learning deficits.
“The elevated level of follicle-stimulating hormone (FSH) directly promotes the accumulation of Aβ and hyperphosphorylated tau in the hippocampus via the C/EBPβ-δ secretase pathway, leading to neuronal apoptosis, synaptic damage and spatial learning deficits.353”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [353]
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Retracted
- Authors
- Xiong, J., Kang, S. S., Wang, Z., Liu, X., Kuo, T.-C., Korkmaz, F., Padilla, A., Miyashita, S., Chan, P., Zhang, Z., Katsel, P., Burgess, J., Gumerova, A., Ievleva, K., Sant, D., Yu, S.-P., Muradova, V., Frolinger, T., Lizneva, D., Iqbal, J., Goosens, K. A., Gera, S., Rosen, C. J., Haroutunian, V., Ryu, V., Yuen, T., Zaidi, M., & Ye, K.
- Affiliations
- Emory University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Renmin Hospital of Wuhan University (CN)
- Maine Medical Center Research Institute (US)
- Corresponding author
- Zaidi, Mone
- Ye, Keqiang
- ORCID
- Xiong, Jing
- Kang, Seong Su
- Liu, Xia
- Kuo, Tan-Chun
- Korkmaz, Funda
- Padilla, Ashley
- Zhang, Zhaohui
- Katsel, Pavel
- Gumerova, Anisa
- Ievleva, Kseniia
- Yu, Shan-Ping
- Muradova, Valeriia
- Frolinger, Tal
- Lizneva, Daria
- Iqbal, Jameel
- Goosens, Ki A.
- Gera, Sakshi
- Rosen, Clifford J.
- Haroutunian, Vahram
- Ryu, Vitaly
- Yuen, Tony
- Zaidi, Mone
- Ye, Keqiang
- Venue
- Nature
- Published
- 2022-03-02
- Volume
- 603
- Issue
- 7901
- Pages
- 470-476
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC9940301
- OpenAlex
- W4214944386
- Cited by
- 329
- References
- 66
- Citations by year
- 2026: 48 · 2025: 78 · 2024: 89 · 2023: 75 · 2022: 39
- FWCI
- 43.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (UL1TR002378)
- National Institute on Aging (R01AG065177, RF1AG051538, R01AG071870, U19AG060917, U01AG073148, R01AG074092, P30AG066514)
- National Institute of General Medical Sciences (P20GM121301)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK113627)
- National Institute of Neurological Disorders and Stroke (P30NS055077)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- follicle-stimulating hormone, Alzheimer's disease, menopause, amyloid-beta deposition, tau deposition, cognitive impairment, hippocampal neurons, cortical neurons, obesity, osteoporosis, dyslipidemia, energy homeostasis
- MeSH terms
- Aged, Alzheimer Disease, Animals, Cognition, Female, Follicle Stimulating Hormone, Humans, Bone Density, Thermogenesis, Mice
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