{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:58Z","timestamp":1787026558292,"version":"build-2736575974"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"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>Alzheimer\u2019s disease (AD) remains a major therapeutic challenge despite the availability of amyloid-targeting disease-modifying therapies for selected patients with early symptomatic disease. These therapies have shown that disease modification is possible, but their benefits are modest and constrained by amyloid confirmation, safety monitoring, infusion delivery, access, and eligibility requirements. Neuroinflammation is increasingly viewed as a context-dependent modifying process that interacts with \u03b2-amyloid (A\u03b2), tau pathology, metabolic stress, and vascular dysfunction, rather than as an unequivocally established primary initiating driver. This review provides a selective, glia-centered synthesis of AD neuroinflammation focused on microglia, astrocytes, and their reciprocal crosstalk. We examine how microglial and astrocytic responses can support A\u03b2 handling, plaque containment, tissue homeostasis, and synaptic protection, while chronic or poorly resolved glial signaling can amplify cytokine and complement responses, metabolic and oxidative stress, and neuronal vulnerability. Representative signaling nodes, including NF-\u03baB, AMPK\/mTOR, and PI3K\/Akt, are discussed as organizing mechanisms linking inflammatory transcription, proteostatic stress, glial metabolism, and neuronal injury, rather than as equivalently validated therapeutic targets. Therapeutic implications are interpreted across three evidence tiers: approved anti-amyloid antibodies with indirect inflammatory relevance, clinically tested anti-inflammatory or immunomodulatory strategies that have not established disease-modifying efficacy, and experimental precision approaches aimed at glial-state modulation. Overall, the translational challenge is not broad suppression of neuroinflammation, but stage-specific identification and modulation of maladaptive glial states while preserving protective microglial and astrocytic functions.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1783786","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:53:15Z","timestamp":1780030395000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuroinflammation in Alzheimer\u2019s disease: glial crosstalk, pathological modulation, and therapeutic implications"],"prefix":"10.3389","volume":"17","author":[{"given":"Enhao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Chongqing University Three Gorges Hospital, Chongqing University","place":["Chongqing, 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