{
  "abstract": "Nasu-Hakola disease (NHD), a dementia with about 200 cases worldwide, is caused by loss-of-function mutation of TYROBP, encoding DAP12, or its receptor TREM2. TREM2-DAP12 is the switch that converts microglia from a surveillant to a reactive state; what DAP12-deficient microglia become and to what extent they reshape their microenvironment is unknown. We profiled prefrontal cortex and hippocampus from an NHD donor and control by single-nucleus RNA sequencing and mapped the glial changes in situ by spatial transcriptomics. NHD microglia adopted a CIITA-driven, MHC class II-high antigen-presenting state with complement, iron and glycolytic programs and Fc receptors but not the TREM2-dependent lipid program. Astrocytes became pan-reactive and lost metallothionein expression, oligodendrocytes lost mature cells and cholesterol synthesis, and excitatory neurons lost presynaptic and activity programs, consistently between regions and across a published cohort. DAP12 deficiency left microglia in an antigen-presenting state short of the TREM2-dependent arm, accompanied by a glial-to-neuronal cascade.",
  "abstract_shown": true,
  "affiliations": [
    "RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "J. Leon"
    },
    {
      "name": "S. Yoshinaga"
    },
    {
      "name": "I. Koya"
    },
    {
      "name": "G. Palafox"
    },
    {
      "name": "Y. Ando"
    },
    {
      "name": "K.-i. Kubo"
    },
    {
      "name": "J. Moody"
    },
    {
      "name": "M. Takao"
    },
    {
      "name": "P. Carninci"
    },
    {
      "name": "J. Shin"
    },
    {
      "name": "C. Condello"
    },
    {
      "name": "H. Okano"
    },
    {
      "name": "C. C. Hon"
    },
    {
      "name": "S. Morimoto"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2880t8wqwbmpf.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.07.757387",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757387v1.full",
  "id": "2880t8wqwbmpf",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757387v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2808|Neuroinflammation and Neurodegeneration Mechanisms"
    ]
  ],
  "openalex": "W7221453454",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757387v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2880t8wqwbmpf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:10Z",
      "native_id": "10.64898/2026.10.07.757387",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757387v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "DAP12-deficient microglia adopt a TREM2-independent antigen-presenting state with a glial-to-neuronal cascade in Nasu-Hakola disease",
  "title_text": "DAP12-deficient microglia adopt a TREM2-independent antigen-presenting state with a glial-to-neuronal cascade in Nasu-Hakola disease",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:10Z",
  "url": "https://research.draconitic.com/paper/2880t8wqwbmpf",
  "venue": "bioRxiv",
  "versions": []
}