{
  "abstract": "P2x purinoreceptor 7 (P2RX7), an ATP-gated ion channel, is known to play pivotal roles in the progression of Alzheimer's disease (AD), although its cell type-specific pathological mechanisms have yet to be elucidated. Here, we show that genetic deletion of P2rx7 mitigates brain atrophy, tau accumulation and cognitive impairment in PS19 tauopathy mice. Specific deletion of P2rx7 in microglia, but not astrocytes, significantly suppresses tau propagation from the entorhinal cortex to CA1 in the hippocampus, an early event in AD pathology. Single-cell (sc)-RNA sequencing of mouse brains revealed specific P2rx7 expression in microglia, inducing inflammatory changes accompanied by elevated extracellular vesicles (EVs) secretion in PS19 mice. Brain-derived EVs (BDEVs) proteome demonstrated that P2RX7 increases EV cargo loading of tau and mitochondrial molecules in BDEVs from PS19 mice, which was further validated by single-molecule super-resolution. Notably, following the injection of BDEVs isolated from PS19 mice with or without P2rx7 deficiency, the microglial transcriptome of recipient mice revealed enriched DNA-sensing and type II interferon signaling in response to BDEVs from PS19 mice, which was diminished in the group injected with P2rx7-deficient BDEVs. Thus, our results indicate that P2RX7 regulates EV-mediated tau and mitochondrial transfer and inflammatory activation in microglia with increased EV secretion, thereby contributing to tauopathy and neurodegeneration, highlighting the therapeutic potential of targeting the P2RX7-EV axis in AD.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA",
    "Mayo Clinic Florida",
    "Mayo Clinic",
    "Mayo Clinic Floria",
    "Division of Computational Biology, Mayo Clinic, Rochester, MN 55905, USA",
    "Mayo Clinic Jacksonville",
    "Mayo Clinic Rochester",
    "Mass Spectrometry Facility, University of Massachusetts Chan Medical School, Shrewsbury, MA 01545, USA; Department of Biochemistry and Molecular Biotechnology, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA",
    "University of Massachusetts Chan Medical School",
    "Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada",
    "UMASS Chan Medical School",
    "Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Gene Lay Institute of Immunology and Inflammation, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA",
    "University of Toronto",
    "Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School",
    "Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA. Electronic address: ikezu.seiko@mayo.edu",
    "Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA; Robert and Alene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA; Alzheimer's Disease Research Center, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: ikezu.tsuneya@mayo.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Victor Bodart‐Santos",
      "orcid": "0000-0003-0472-6119"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Arun Reddy Ravula"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yang You",
      "orcid": "0000-0003-0574-7827"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Mohammad Abdullah"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhi Ruan",
      "orcid": "0000-0003-3587-9425"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "J. W Ellison"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Stephanie Radhakishun"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nibedita Basu Ray"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Bridgette C. Melvin"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Aishe Kurti"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Zhewei Liang"
    },
    {
      "affs": [
        4,
        2
      ],
      "name": "Yuta Sakai"
    },
    {
      "affs": [
        4,
        6
      ],
      "name": "Daniel R. O’Brien"
    },
    {
      "affs": [
        7,
        2
      ],
      "name": "Son N. Nguyen"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Scott A. Shaffer",
      "orcid": "0000-0002-5264-3257"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "Lindsey Fiddes"
    },
    {
      "affs": [
        11,
        12
      ],
      "name": "Oleg Butovsky",
      "orcid": "0000-0003-0186-8867"
    },
    {
      "affs": [
        0,
        13
      ],
      "name": "Wolfdieter Springer",
      "orcid": "0000-0002-1178-3149"
    },
    {
      "affs": [
        14,
        1
      ],
      "name": "Seiko Ikezu",
      "orcid": "0000-0001-9879-730X"
    },
    {
      "affs": [
        15,
        1
      ],
      "name": "Seiko Ikezu",
      "orcid": "0000-0001-9879-730X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/66ykgn184cnsx.bib",
  "cited_by": 6,
  "doi": "10.1016/j.neuron.2026.10.007",
  "fulltext_url": null,
  "id": "66ykgn184cnsx",
  "issns": [
    "0896-6273",
    "1097-4199"
  ],
  "landing_url": "https://doi.org/10.1016/j.neuron.2026.10.007",
  "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",
      "2804|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W4411555888",
  "pdf_url": "https://www.cell.com/neuron/pdf/S0896-6273(26)00777-4.pdf",
  "pmcid": "PMC12270207",
  "pmid": "40678243",
  "published": "2026-11-01",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/66ykgn184cnsx.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T13:20:36Z",
      "native_id": "W4411555888",
      "source": "openalex",
      "url": "https://doi.org/10.1016/j.neuron.2026.10.007"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Alzheimer's disease research and treatments",
      "subfield": "neuroscience"
    }
  ],
  "title": "P2RX7 drives inflammatory microglia and pathogenic extracellular vesicle secretion in tauopathy",
  "title_text": "P2RX7 drives inflammatory microglia and pathogenic extracellular vesicle secretion in tauopathy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:14Z",
  "url": "https://research.draconitic.com/paper/66ykgn184cnsx",
  "venue": "Neuron",
  "versions": []
}