2. Academic Validation
  3. IL-24 ameliorates cognitive dysfunction via the inhibition PERK-eIF2α Signaling pathway in Alzheimer's disease

IL-24 ameliorates cognitive dysfunction via the inhibition PERK-eIF2α Signaling pathway in Alzheimer's disease

  • Int Immunopharmacol. 2026 Jan 15:169:116039. doi: 10.1016/j.intimp.2025.116039.
Yansheng Du 1,  Xiaolei Zheng 2,  Xinyi Yue 3,  Pengrun Fu 2,  Jiuzhou Diao 4,  Anna Zhang 4,  Haoyang Cheng 2,  Hui Yang 2,  Jianzhong Bi 2,  Qingbo Zhou 5,  Ping Wang 6
Affiliations

Affiliations

  • 1 Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
  • 2 Department of Neurology Medicine, The Second Hospital of Shandong University, Jinan, China.
  • 3 Department of Neurology Medicine, Shandong Public Health Clinical Center, Shandong University, Jinan, China.
  • 4 Department of Geriatrics, South Branch of The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
  • 5 Geriatric Medicine Center, Affiliated Hospital of Shandong University of TCM, Jinan, China. Electronic address: [email protected].
  • 6 Department of Neurology Medicine, The Second Hospital of Shandong University, Jinan, China. Electronic address: [email protected].
PMID: 41411732 DOI: 10.1016/j.intimp.2025.116039
Abstract

The role of inflammation in the etiology and progression of Alzheimer's disease (AD) has attracted increasing attention; however, the effect of peripheral adaptive immune cells and IL-24 expression on amnestic mild cognitive impairment (aMCI)/AD remains unclear. We detected a reduction in CD4+ central memory T cells (TCM) and an increase in effector memory T cells (TEM) in AD compared with aMCI and controls. CD4+ T cells from patients with AD showed enhanced proliferation, reduced secretion levels of IL-24, and increased secretion levels of IFN-γ and TNF-α. The decrease in IL-24 expression in patients with AD was positively associated with cognition. IL-24 overexpression significantly ameliorated the cognitive deficits, neuropathological injury, and cytotoxicity in AD in vivo and in vitro, potentially through PERK-eIF2α pathway inhibition. Altogether, T cell subset analyses supported a shift towards senescence of the adaptive immune system in AD. IL-24 is a new therapeutic target and strategy for AD.

Keywords

Alzheimer's disease; Amnestic mild cognitive impairment; Endoplasmic reticulum stress; Interleukin-24; T cell subsets.

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