{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:46:24Z","timestamp":1791733584921,"version":"4.3.4"},"reference-count":0,"publisher":"Aging and Disease","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Dis"],"abstract":"<jats:p>Neuroimmune mechanisms are central to Alzheimer\u2019s disease (AD), but a single continuum of \u201cmore inflammation\u201d does not explain why similar amyloid-\u03b2 (A\u03b2) and tau burdens are associated with different clinical trajectories, tissue responses, and treatment risks. We present a testable neuroimmune-state framework that integrates, rather than replaces, the AT(N) system, cellular-phase models, and transcriptional descriptions of disease-associated microglia and reactive astrocytes. The framework treats neuroimmune states as multidimensional, regionally heterogeneous configurations defined by pathological substrate, cellular program, biological target, vascular and aging context, and measurable patient-level readouts. We distinguish four meanings of the amyloid-tau interface: a biomarker interface, a spatial tissue interface, a cellular-state interface, and a clinical-progression interface. We then examine the hypothesis of phagocytic target switching, in which clearance pathways that support plaque compaction or debris removal may, under selected tau- and complement-rich conditions, contribute to removal of stressed but potentially functional synapses. We explicitly separate evidence from longitudinal human studies, cross-sectional biomarkers, human genetics, postmortem tissue, animal models, and in vitro systems. Current biomarkers cannot yet assign patients to validated discrete neuroimmune states; proposed state readers should therefore be probabilistic, allow regional coexistence and parallel vascular-immune trajectories, and be tested for incremental value beyond established AD biomarkers and co-pathologies. Finally, we organize immune-directed interventions by clinical evidence level and frame stage matching as a research strategy rather than a treatment algorithm. The model is useful only if its predictions can be prospectively supported or falsified.<\/jats:p>","DOI":"10.14336\/ad.2026.0888","type":"journal-article","created":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:02:20Z","timestamp":1791730940000},"source":"Crossref","is-referenced-by-count":0,"title":["Neuroimmune State Configurations at the Amyloid-Tau Interface in Alzheimer\u2019s Disease: A Testable Framework"],"prefix":"10.14336","member":"5462","published-online":{"date-parts":[[2026]]},"container-title":["Aging and Disease"],"original-title":[],"deposited":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:02:22Z","timestamp":1791730942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.aginganddisease.org\/EN\/10.14336\/AD.2026.0888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":0,"URL":"https:\/\/doi.org\/10.14336\/ad.2026.0888","relation":{},"ISSN":["2152-5250"],"issn-type":[{"value":"2152-5250","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]}}}