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
  • 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.
Products
Inhibitors & Agonists
Other Products