{
  "abstract": "Cerebrovascular disease is a major but poorly understood feature of Alzheimer's disease (AD). The strongest genetic AD risk factor, apolipoprotein E4 (APOE4), is associated with cerebrovascular degeneration, including vascular amyloid deposition and fibrosis. To uncover how APOE4 promotes cerebrovascular pathology, we assembled a single-cell transcriptomic atlas of human brain vasculature. In APOE4 carriers, pericyte abundance was significantly reduced and accompanied by the emergence of a myofibroblast-like cell population co-expressing contraction and extracellular matrix genes. Immunostaining confirmed non-vascular myofibroblasts in APOE4 human and mouse brains. We show that APOE4 pericytes transition into myofibroblasts that secrete fibronectin, which promotes vascular amyloid accumulation. Computational and experimental analyses identified elevated transforming growth factor β (TGF-β) signaling as the driver of this pericyte-to-myofibroblast transition. Inhibition of TGF-β restored pericyte coverage and reduced vascular fibrosis and amyloid to APOE3 levels, revealing a targetable mechanism linking APOE4 to cerebrovascular pathology in AD.",
  "abstract_shown": true,
  "affiliations": [
    "Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.",
    "Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.",
    "Institute for Regenerative Medicine, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA",
    "Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Braxton R. Schuldt"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Dominic Haworth-Staines"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Andrea Perez-Arevalo"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Diede W.M. Broekaart"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ashley Harlock"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Leon Wang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Anna Bright"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Georgia Gallagher"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Grace Rabinowitz"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Alison M. Goate"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Towfique Raj"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Ana C. Pereira"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Joel W. Blanchard"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aramvmdp1ehby.bib",
  "cited_by": 0,
  "doi": "10.1016/j.cell.2026.08.058",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13698807/",
  "id": "aramvmdp1ehby",
  "issns": [
    "0092-8674",
    "1097-4172"
  ],
  "landing_url": "https://doi.org/10.1016/j.cell.2026.08.058",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2808|Barrier Structure and Function Studies"
    ]
  ],
  "openalex": "W7214176885",
  "pdf_url": null,
  "pmcid": "PMC13698807",
  "pmid": "42785300",
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/aramvmdp1ehby.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:34Z",
      "native_id": "PMC13698807",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.cell.2026.08.058"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Barrier Structure and Function Studies",
      "subfield": "neurology"
    }
  ],
  "title": "A pericyte-to-myofibroblast transition links APOE4 to cerebrovascular degeneration",
  "title_text": "A pericyte-to-myofibroblast transition links APOE4 to cerebrovascular degeneration",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:35:30Z",
  "url": "https://research.draconitic.com/paper/aramvmdp1ehby",
  "venue": "Cell",
  "versions": []
}