2026-10-14T06:11:05Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34041861 2026-10-01T09:36:37Z category_696 portal_316 item_type_3 month_year_10_2026

Table 1_CD8+ t cell-mediated regulation of synaptic integrity in Alzheimer’s disease.docx Hua Fu (178428) Jing Yang (13969) Miao Zhang (17216) Genetic Immunology Alzheimer’s disease CD8+ T cells complement cascade granzyme K MHC class I microglia neuroimmunology synaptic integrity <p>Alzheimer’s disease (AD) has traditionally been interpreted through amyloid, tau, and innate immune frameworks, with the complement cascade long regarded as the principal driver of aberrant synaptic pruning. Synaptic loss is increasingly recognized as one of the strongest correlates of cognitive decline. This review examines an emerging CD8⁺ T cell–synapse axis that extends beyond complement-centric models. We discuss how brain-infiltrating CD8⁺ T cells intersect with synaptic integrity through MHC-I-dependent and MHC-I-independent mechanisms, including IFN-γ–mediated microglial reprogramming and granzyme K–driven non-canonical complement activation. Early effector-like subsets may promote neuroinflammation and synaptic injury, whereas later tissue-resident or regulatory populations can exert protective functions by gating microglial states. The net outcome depends on disease stage, antigenic milieu, anatomical niche, and microglial context. We emphasize that direct antigen-specific, MHC-I-restricted synaptic attack remains unproven in human AD, and that observed T-cell infiltration may reflect reverse causality. Translational limitations across species are evaluated, and we outline subset-specific immunomodulation, ApoE4-stratified strategies, and biomarker-guided trial designs as future directions. Overall, CD8⁺ T cells are positioned not as uniform cytotoxic executors, but as dynamic, context-dependent regulators of synaptic outcomes in AD.</p> 2026-10-01T09:36:37Z Dataset Dataset 10.3389/fimmu.2026.1903001.s001 https://figshare.com/articles/dataset/Table_1_CD8_t_cell-mediated_regulation_of_synaptic_integrity_in_Alzheimer_s_disease_docx/34041861 CC BY 4.0