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

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 (T_CM) and an increase in effector memory T cells (T_EM) 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.