{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:00:25Z","timestamp":1790848825501,"version":"4.1.0"},"reference-count":117,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Alzheimer\u2019s 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\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013synapse axis that extends beyond complement-centric models. We discuss how brain-infiltrating CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells intersect with synaptic integrity through MHC-I-dependent and MHC-I-independent mechanisms, including IFN-\u03b3\u2013mediated microglial reprogramming and granzyme K\u2013driven 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\n                    <jats:sup>+<\/jats:sup>\n                    T cells are positioned not as uniform cytotoxic executors, but as dynamic, context-dependent regulators of synaptic outcomes in AD.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1903001","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:45:55Z","timestamp":1790847955000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CD8+ t cell-mediated regulation of synaptic integrity in Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Hua","family":"Fu","sequence":"first","affiliation":[{"name":"The Second Clinical Medical College, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"The Second Clinical Medical College, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2025.1683158","article-title":"Trends and cross-country inequalities in the global burden of alzheimer\u2019s disease and other dementias among adults aged 65+ years, 1990-2021: a population based study with projections into 2050","volume":"17","author":"Liu","year":"2025","journal-title":"Front Aging Neurosci"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(24)00264-X","article-title":"The global macroeconomic burden of 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