CD103^-CD8⁺ T cells promote neurotoxic inflammation in Alzheimer's disease via granzyme K-PAR-1 signaling.

ABSTRACT: Immune mechanisms contribute to the neuropathology of Alzheimer's disease (AD) but the role of adaptive immune cells is unclear. Here we show that the brain CD8⁺ T cell compartment is dysregulated in AD patients and in the 3xTg-AD mouse model, accumulating activated CD103^- tissue-resident memory T cells that produce large amounts of granzyme K (GrK). These CD103^-CD8⁺ T cells originate from the circulation and migrate into the brain using LFA-1 integrin. Ablation of brain CD103^-CD8⁺ T cells in 3xTg-AD mice ameliorates cognitive decline and reduces neuropathology. GrK induces neuronal dysfunction and tau hyperphosphorylation in human and mouse cells via protease-activated receptor-1 (PAR-1), which is expressed at higher levels

SUBMITTER: Terrabuio E 

PROVIDER: S-EPMC12460627 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature