{
  "abstract": "Alzheimer's 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-State-Space 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.",
  "abstract_shown": true,
  "affiliations": [
    "Hwamei College of Life and Health Sciences, Zhejiang Wanli University, Ningbo 315100, China",
    "Zhejiang Key Laboratory of Intelligent Food Logistic and Processing, Yuyao Innovation Institute, Zhejiang Wanli University, Ningbo 315400, China"
  ],
  "article_type": "review",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xiaopu Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Xingyu Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiaxing Dou"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiahui Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Feng Xue",
      "orcid": "0000-0002-5058-5735"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0dz9a95zm1sfw.bib",
  "cited_by": 5,
  "doi": "10.3390/cells15131208",
  "fulltext_url": null,
  "id": "0dz9a95zm1sfw",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://doi.org/10.3390/cells15131208",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2808|Neuroinflammation and Neurodegeneration Mechanisms"
    ]
  ],
  "openalex": "W7167069565",
  "pdf_url": "https://www.mdpi.com/2073-4409/15/13/1208/pdf?version=1783003547",
  "pmcid": "PMC13359899",
  "pmid": "42439681",
  "published": "2026-07-02",
  "publisher": "Multidisciplinary Digital Publishing Institute",
  "ris": "https://research.draconitic.com/paper/0dz9a95zm1sfw.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:11Z",
      "native_id": "W7167069565",
      "source": "openalex",
      "url": "https://doi.org/10.3390/cells15131208"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Neuroinflammation and Neurodegeneration Mechanisms",
      "subfield": "neurology"
    }
  ],
  "title": "Rethinking Anti-Inflammatory Therapy in Alzheimer’s Disease: From Broad Suppression to Stage–State–Space Neuroimmune Reprogramming",
  "title_text": "Rethinking Anti-Inflammatory Therapy in Alzheimer’s Disease: From Broad Suppression to Stage–State–Space Neuroimmune Reprogramming",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:14Z",
  "url": "https://research.draconitic.com/paper/0dz9a95zm1sfw",
  "venue": "Cells",
  "versions": []
}