{
  "abstract": "Parkinson's disease (PD) is characterized by the build-up of α-synuclein (α-syn) in the brain, where it drives neurodegeneration. Importantly, aggregated α-syn also accumulates in the cerebrospinal fluid (CSF) of PD patients, and while increasingly used for diagnosis, its pathological role remains poorly understood. Here, we demonstrate that α-syn accumulation in central nervous system (CNS) border tissues promotes CNS clearance deficits, as observed in PD patients. We find that aggregated α-syn accumulates not only in the CSF but also in the dura mater of individuals with PD, and, using acute and chronic mouse models, show that α-syn deposition in these sites induces immune alterations in CNS borders and disrupts CNS clearance. Mechanistically, we reveal that α-syn at CNS borders elevates CSF TNF and demonstrate that both TNF and α-syn aggregates themselves impair lymphatic endothelial cell function. These findings demonstrate a pathological role for α-syn in the CNS border tissues and position meningeal immunity as a contributor to CNS clearance deficits in PD pathogenesis.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Auckland, New Zealand.",
    "Centre for Brain Research, The University of Auckland , Auckland, New Zealand.",
    "Department of Anatomy and Medical Imaging, The University of Auckland, Auckland, New Zealand.",
    "LabPlus, Department of Anatomical Pathology, Te Whatu Ora, Auckland, New Zealand."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Taylor J Stevenson",
      "orcid": "0000-0001-6032-1445"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Luca Vinnell",
      "orcid": "0009-0000-0864-3236"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Samuel J C McCullough",
      "orcid": "0009-0001-7867-7025"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Daniel X Flyger",
      "orcid": "0009-0000-0461-4016"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Blake Highet",
      "orcid": "0009-0002-5369-0554"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "James A Wiseman",
      "orcid": "0000-0001-9880-1612"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ben Watkin",
      "orcid": "0009-0003-4291-6017"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kate Hitpass Romero",
      "orcid": "0009-0008-4806-3517"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Victoria F Low",
      "orcid": "0009-0002-6490-0852"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Amy M Smith",
      "orcid": "0000-0002-8912-4741"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Angela Wu",
      "orcid": "0000-0002-8349-8427"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Dahna M Fong",
      "orcid": "0000-0003-3988-925X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Natasha L Grimsey",
      "orcid": "0000-0003-3941-4537"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Birger V Dieriks",
      "orcid": "0000-0002-9392-3327"
    },
    {
      "affs": [
        3
      ],
      "name": "Clinton P Turner",
      "orcid": "0000-0002-2138-7633"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Deborah Young",
      "orcid": "0000-0003-1085-2824"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Maurice A Curtis",
      "orcid": "0000-0003-4496-0233"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Richard L M Faull",
      "orcid": "0000-0003-3385-9498"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mike Dragunow",
      "orcid": "0000-0003-1711-1631"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Justin Rustenhoven",
      "orcid": "0000-0002-9376-7424"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/85ywtn0fajrn4.bib",
  "cited_by": 1,
  "doi": "10.1084/jem.20251245",
  "fulltext_url": "https://europepmc.org/articles/PMC13682444",
  "id": "85ywtn0fajrn4",
  "issns": [
    "0022-1007",
    "1540-9538"
  ],
  "landing_url": "https://europepmc.org/article/MED/42900184",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7223046623",
  "pdf_url": "https://europepmc.org/articles/PMC13682444?pdf=render",
  "pmcid": "PMC13682444",
  "pmid": "42900184",
  "published": "2026-10-20",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/85ywtn0fajrn4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42900184",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42900184"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "Cerebrospinal fluid and dural accumulation of α-synuclein impairs CNS clearance in Parkinson's disease.",
  "title_text": "Cerebrospinal fluid and dural accumulation of α-synuclein impairs CNS clearance in Parkinson's disease.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:32Z",
  "url": "https://research.draconitic.com/paper/85ywtn0fajrn4",
  "venue": "The Journal of experimental medicine",
  "versions": []
}