{
  "abstract": "Identifying individuals at risk for neurodegeneration is a priority for clinical trials. Parkinson's Precision Medicine Initiative (PPMI) deploys strategies to enroll individuals before typical clinical Parkinson's disease symptoms: recruiting polysomnogram-confirmed REM sleep behavior disorder (RBD) and central identification of hyposmia via smell testing. Groups were divided into RBD with and without hyposmia (RBD+Hyposmia, RBD-Hyposmia) and hyposmia with and without self-reported dream enactment behavior (Hyposmia+DEB, Hyposmia-DEB). Participants underwent clinical and biomarker testing including CSF alpha-synuclein seed amplification assay (CSFaSynSAA) and dopamine transporter imaging. While all enrollment strategies showed robust enrichment for CSFaSynSAA positivity, RBD+Hyposmia and Hyposmia+DEB were more likely CSFaSynSAA+ (94% and 85%) vs RBD-Hyposmia (40%) and Hyposmia-DEB (55%). Among CSFaSynSAA+, RBD+Hyposmia and Hyposmia+DEB had more mood, autonomic, and cognitive symptoms than Hyposmia-DEB. PPMI identified a large biologically-defined early neuronal synucleinopathy cohort and demonstrated biomarker and multi-domain clinical heterogeneity within CSFaSynSAA+ individuals prior to symptom onset.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, University of California San Francisco, San Francisco, CA, USA"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "E. G. Brown"
    },
    {
      "name": "H. Blumenau"
    },
    {
      "name": "D.-E. Lafontant"
    },
    {
      "name": "A. R. Nair"
    },
    {
      "name": "N. Johnson"
    },
    {
      "name": "R. N. Alcalay"
    },
    {
      "name": "L. M. Chahine"
    },
    {
      "name": "C. S. Coffey"
    },
    {
      "name": "R. D. Dobkin"
    },
    {
      "name": "T. Foroud"
    },
    {
      "name": "D. Galasko"
    },
    {
      "name": "K. Merchant"
    },
    {
      "name": "B. Mollenhauer"
    },
    {
      "name": "K. L. Poston"
    },
    {
      "name": "A. Siderowf"
    },
    {
      "name": "C. M. Tanner"
    },
    {
      "name": "D. Weintraub"
    },
    {
      "name": "K. Marek"
    },
    {
      "name": "T. Simuni"
    },
    {
      "name": "T. F. Tropea"
    },
    {
      "name": "Parkinson's Precision Medicine Initiative"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/30d94csk6qcsm.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.26.26366535",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.26.26366535v1.full",
  "id": "30d94csk6qcsm",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.26.26366535v1",
  "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": [
    [
      "medrxiv",
      "neurology"
    ],
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7224086409",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.26.26366535v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/30d94csk6qcsm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:58Z",
      "native_id": "10.64898/2026.10.26.26366535",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.26.26366535v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:neurology",
      "subfield": "neurology"
    }
  ],
  "title": "Strategies to establish a biologically defined Parkinson's disease cohort prior to the onset of clinically significant motor symptoms",
  "title_text": "Strategies to establish a biologically defined Parkinson's disease cohort prior to the onset of clinically significant motor symptoms",
  "type": "preprint",
  "updated_at": "2026-10-30T12:21:58Z",
  "url": "https://research.draconitic.com/paper/30d94csk6qcsm",
  "venue": "medRxiv",
  "versions": []
}