C/EBPβ/AEP Signaling Drives Alzheimer's Disease Pathogenesis

Neurosci Bull. 2023 Jul;39(7):1173-1185. doi: 10.1007/s12264-023-01025-w. Epub 2023 Feb 3.

Abstract

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.

Keywords: Alzheimer’s disease; Asparagine endopeptidase; C/EBPβ; Follicle stimulating hormone; Pathogenesis.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / pathology
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cognitive Dysfunction* / metabolism
  • Female
  • Follicle Stimulating Hormone
  • Humans
  • Male
  • Signal Transduction

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Follicle Stimulating Hormone