{
  "abstract": "Extracellular vesicles (EVs) are emerging as key mediators of intercellular communication and potential biomarkers in Parkinson's disease (PD), yet how disease-causing genetic alterations shape neuronal EV biology remains incompletely understood. Here, we used PD-patient iPSC-derived midbrain dopaminergic neurons (mDANs) harboring SNCA triplication (SNCA-4x), gene-corrected controls (SNCA-GC), and SNCA knockout (SNCA-KO) to investigate the impact of -synuclein overexpression on neuronal-enriched EV (nEV) biology and neuron to microglia communication. SNCA-4x mDANs exhibited marked transcriptional alterations in pathways related to vesicle trafficking and extracellular matrix organization. Using an optimized isolation workflow, SNCA-4x neurons released significantly more and smaller nEVs enriched in -synuclein, mitochondrial DNA (mtDNA), and PARK7/DJ-1 mRNA, while displaying reduced acetylcholinesterase activity. Functionally, SNCA-4x-derived nEVs were taken up more efficiently by isogenic control iPSC-derived microglia than SNCA-GC nEVs and induced stronger pro-inflammatory activation than both SNCA-GC nEVs and untreated microglia, characterized by altered microglial morphology and increased TNF- and IL-1{beta}, consistent with damage-associated molecular pattern (DAMP)-mediated signaling. Together, these findings demonstrate that SNCA-4x reshapes the properties and molecular cargo of nEVs, enhancing their capacity to trigger microglial activation, and identify EV-associated -synuclein, mtDNA, and PARK7 mRNA as candidate mechanistic and biomarker features in PD.",
  "abstract_shown": true,
  "affiliations": [
    "LCSB"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "I. Boumpoureka"
    },
    {
      "name": "J. Heider"
    },
    {
      "name": "S. Delcambre"
    },
    {
      "name": "F. B. Kleine Borgmann"
    },
    {
      "name": "A. Poret"
    },
    {
      "name": "I. Boussaad"
    },
    {
      "name": "J. H. Wilbertz"
    },
    {
      "name": "P. Sommer"
    },
    {
      "name": "M. Mittelbronn"
    },
    {
      "name": "A. Gruenewald"
    },
    {
      "affs": [
        0
      ],
      "name": "V. Gorgogietas"
    },
    {
      "name": "R. Krueger"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9jsc8xr5hdn0r.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.09.750343",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750343v1.full",
  "id": "9jsc8xr5hdn0r",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750343v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "1312|Extracellular vesicles in disease"
    ]
  ],
  "openalex": "W7213320481",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750343v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9jsc8xr5hdn0r.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:32Z",
      "native_id": "10.64898/2026.09.09.750343",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.09.750343v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "SNCA triplication shapes neuronal extracellular vesicle biology and promotes microglial activation in patient-derived iPSC-based models of Parkinson's disease",
  "title_text": "SNCA triplication shapes neuronal extracellular vesicle biology and promotes microglial activation in patient-derived iPSC-based models of Parkinson's disease",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:32Z",
  "url": "https://research.draconitic.com/paper/9jsc8xr5hdn0r",
  "venue": "bioRxiv",
  "versions": []
}