{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:29:00Z","timestamp":1793158140970,"version":"4.5.0"},"reference-count":71,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006579","name":"Ministry of Industry and Information Technology","doi-asserted-by":"publisher","award":["20231023"],"award-info":[{"award-number":["20231023"]}],"id":[{"id":"10.13039\/501100006579","id-type":"DOI","asserted-by":"publisher"}]},{"award":["20231023"],"award-info":[{"award-number":["20231023"]}],"id":[{"id":"https:\/\/ror.org\/0385nmy68","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009106","name":"Zhejiang Wanli University","doi-asserted-by":"publisher","award":["DZS2026009"],"award-info":[{"award-number":["DZS2026009"]}],"id":[{"id":"10.13039\/100009106","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009106","name":"Zhejiang Wanli University","doi-asserted-by":"publisher","award":["SC1032511980070"],"award-info":[{"award-number":["SC1032511980070"]}],"id":[{"id":"10.13039\/100009106","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009106","name":"Zhejiang Wanli University","doi-asserted-by":"publisher","award":["JT2680100001"],"award-info":[{"award-number":["JT2680100001"]}],"id":[{"id":"10.13039\/100009106","id-type":"DOI","asserted-by":"publisher"}]},{"award":["DZS2026009"],"award-info":[{"award-number":["DZS2026009"]}],"id":[{"id":"https:\/\/ror.org\/00rjdhd62","id-type":"ROR","asserted-by":"publisher"}]},{"award":["SC1032511980070"],"award-info":[{"award-number":["SC1032511980070"]}],"id":[{"id":"https:\/\/ror.org\/00rjdhd62","id-type":"ROR","asserted-by":"publisher"}]},{"award":["JT2680100001"],"award-info":[{"award-number":["JT2680100001"]}],"id":[{"id":"https:\/\/ror.org\/00rjdhd62","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alzheimer\u2019s Disease (AD) is now understood as a biologically diverse condition, with amyloid and tau pathology evolving within dynamic neuroimmune networks. This challenges the traditional view that AD-related inflammation can be broadly suppressed therapeutically. We review evidence showing that neuroinflammation in AD is stage-dependent, cell-state-specific, spatially organized, and functionally complex. Microglia and astrocytes can aid in plaque containment, debris clearance, synaptic balance, metabolic adaptation, and tissue repair, but may also exacerbate injury through type-I interferon, inflammasome, complement, tumor necrosis factor, and lipid pathways. Many failed anti-inflammatory trials likely stem from mismatches in targets, timing, spatial considerations, pathway redundancy, and biomarker selection, rather than invalidating neuroinflammation as a therapeutic target. Recent single-cell and spatial transcriptomic, proteomic, metabolomic, and network-medicine studies offer a framework for precision intervention by identifying inflammatory endotypes, anatomical niches, and pathway modules. We propose the Stage\u2013State\u2013Space Neuroimmune Reprogramming Model (S3-NRM), aligning AD immunotherapy with disease stage, glial\/endotype state, and spatial inflammatory niche, guided by fluid, imaging, and omics biomarkers. Future therapies should selectively suppress harmful immune responses while preserving beneficial glial functions.<\/jats:p>","DOI":"10.3390\/cells15131208","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T15:52:24Z","timestamp":1783007544000},"page":"1208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Rethinking Anti-Inflammatory Therapy in Alzheimer\u2019s Disease: From Broad Suppression to Stage\u2013State\u2013Space Neuroimmune Reprogramming"],"prefix":"10.3390","volume":"15","author":[{"given":"Xiaopu","family":"Li","sequence":"first","affiliation":[{"name":"Hwamei College of Life and Health Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Hwamei College of Life and Health Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxing","family":"Dou","sequence":"additional","affiliation":[{"name":"Hwamei College of Life and Health Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Wang","sequence":"additional","affiliation":[{"name":"Hwamei College of Life and Health Sciences, Zhejiang Wanli University, Ningbo 315100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5058-5735","authenticated-orcid":false,"given":"Feng","family":"Xue","sequence":"additional","affiliation":[{"name":"Hwamei College of Life and Health Sciences, Zhejiang Wanli University, Ningbo 315100, China"},{"name":"Zhejiang Key Laboratory of Intelligent Food Logistic and Processing, Yuyao Innovation Institute, Zhejiang Wanli University, Ningbo 315400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","unstructured":"Alzheimer\u2019s Association (2025). 2025 Alzheimer\u2019s disease facts and figures. 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