C/EBPβ/AEP Signaling Drives Alzheimer’s Disease Pathogenesis
Open accessAbstract
Alzheimer's disease (AD) is the most common type of dementia. Almost two-thirds of patients with AD are female. The reason for the higher susceptibility to AD onset in women is unclear. However, hormone changes during the menopausal transition are known to be associated with AD. Most recently, we reported that follicle-stimulating hormone (FSH) promotes AD pathology and enhances cognitive dysfunctions via activating the CCAAT-enhancer-binding protein (C/EBPβ)/asparagine endopeptidase (AEP) pathway. This review summarizes our current understanding of the crucial role of the C/EBPβ/AEP pathway in driving AD pathogenesis by cleaving multiple critical AD players, including APP and Tau, explaining the roles and the mechanisms of FSH in increasing the susceptibility to AD in postmenopausal females. The FSH-C/EBPβ/AEP pathway may serve as a novel therapeutic target for the treatment of AD.
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The C/EBPβ-AEP pathway has also been implicated in Alzheimer's disease and Parkinson's disease.
“This pathway has also been implicated in AD and PD.399,400”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [399]
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Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
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“155,156 In PD models, AEP cleaves α-synuclein into toxic fragments, facilitating Lewy body formation and neuronal damage.”
- Authors
- Xiong, J., Zhang, Z., & Ye, K.
- Affiliations
- Renmin Hospital of Wuhan University (CN)
- Shenzhen Institutes of Advanced Technology (CN)
- Corresponding author
- Ye, Keqiang
- Venue
- Neuroscience Bulletin
- Published
- 2023-02-03
- Volume
- 39
- Issue
- 7
- Pages
- 1173-1185
- ISSN
- 1995-8218 (ISSN-L)
- 1673-7067
- PMC
- PMC10313643
- OpenAlex
- W4319057809
- Cited by
- 37
- References
- 135
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 10
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Neuroscience Bulletin (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (82271446)
- 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
- Alzheimer's disease, C/EBPβ, asparaginyl endopeptidase, follicle-stimulating hormone, menopause, postmenopausal women, amyloid precursor protein, tau protein, proteolytic cleavage, cognitive impairment, therapeutic target
- MeSH terms
- Alzheimer Disease, Female, Follicle Stimulating Hormone, Humans, Male, Signal Transduction, CCAAT-Enhancer-Binding Protein-beta, Cognitive Dysfunction
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