{
  "abstract": "Lewy bodies, the defining pathological feature of Parkinson’s disease, are intraneuronal inclusions enriched in aggregated alpha-synuclein (αSyn). We used correlative light and electron microscopy to selectively investigate phosphorylated αSyn (αSyn pS129 )-positive inclusions in the substantia nigra of end-stage postmortem Parkinson’s disease brain. Here we show that somatic αSyn pS129 inclusions in nigral dopaminergic neurons are consistently fibrillar, whereas the membranous-type inclusions are restricted to neuritic processes. These neuritic inclusions displayed marked ultrastructural heterogeneity, ranging from predominantly membranous to mixed membranous-fibrillar forms. The selective targeting of defined inclusions enabled detailed structural characterization of Lewy pathology, rather than quantitative or disease-stage comparisons. Our findings highlight clear ultrastructural differences between somatic and neuritic αSyn pS129 pathology and demonstrate the structural complexity and heterogeneity of Lewy pathology in human Parkinson’s disease brain.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland. amanda.lewis@epfl.ch",
    "Laboratory of Biological Electron Microscopy, School of Basic Sciences, Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland. amanda.lewis@epfl.ch",
    "Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland",
    "Laboratory of Biological Electron Microscopy, School of Basic Sciences, Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland",
    "F. Hoffmann-La Roche Ltd, Pharma Research and Early Development, Grenzacherstrasse 124, Basel, Switzerland",
    "Department of Anatomy and Neurosciences, section Clinical Neuroanatomy and Biobanking, Amsterdam Neuroscience, Amsterdam University Medical Centre, Vrije University Amsterdam, Amsterdam, The Netherlands",
    "Amsterdam Neuroscience program Neurodegeneration, Amsterdam University Medical Centre, Vrije University Amsterdam, Amsterdam, The Netherlands"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Amanda J. Lewis",
      "orcid": "0000-0001-7257-5848"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Lukas van den Heuvel",
      "orcid": "0000-0001-9168-8450"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Marta Di Fabrizio",
      "orcid": "0000-0003-3812-5995"
    },
    {
      "affs": [
        3
      ],
      "name": "Kaliya Bandelier"
    },
    {
      "affs": [
        3
      ],
      "name": "Daria Proniakova"
    },
    {
      "affs": [
        2,
        4,
        3
      ],
      "name": "Domenic Burger",
      "orcid": "0000-0002-4181-2588"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Notash Shafiei",
      "orcid": "0009-0005-4567-9795"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Kazadi Ekundayo",
      "orcid": "0009-0003-1824-0037"
    },
    {
      "affs": [
        3
      ],
      "name": "Selene Offringa",
      "orcid": "0009-0009-1148-2707"
    },
    {
      "affs": [
        5
      ],
      "name": "Evelien Huisman"
    },
    {
      "affs": [
        5
      ],
      "name": "John G. J. M. Bol"
    },
    {
      "affs": [
        6,
        5
      ],
      "name": "Wilma D. J. van de Berg",
      "orcid": "0000-0002-6175-5357"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Henning Stahlberg",
      "orcid": "0000-0002-1185-4592"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7wqwq28marwbv.bib",
  "cited_by": 11,
  "doi": "10.1038/s41467-026-74083-z",
  "fulltext_url": null,
  "id": "7wqwq28marwbv",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://doi.org/10.1038/s41467-026-74083-z",
  "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",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7163879007",
  "pdf_url": null,
  "pmcid": "PMC13396239",
  "pmid": "42259820",
  "published": "2026-06-08",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/7wqwq28marwbv.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T13:20:59Z",
      "native_id": "W7163879007",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41467-026-74083-z"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "Ultrastructural diversity and subcellular organization of nigral Lewy pathology in Parkinson’s disease",
  "title_text": "Ultrastructural diversity and subcellular organization of nigral Lewy pathology in Parkinson’s disease",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:16Z",
  "url": "https://research.draconitic.com/paper/7wqwq28marwbv",
  "venue": "Nature Communications",
  "versions": []
}