{
  "abstract": "The role of peripheral immunity in Parkinsons disease (PD) remains incompletely understood. Here, we performed paired single-cell RNA sequencing (scRNA-seq) and T-cell receptor (TCR) profiling of 630k peripheral blood mononuclear cells (PBMCs) from 168 donors spanning idiopathic and genetic PD, prodromal PD, and healthy controls. We identify broad changes in immune-cell composition across the disease spectrum, including decreased naive B cells and increased naive CD8+ T cells in idiopathic PD. Transcriptional profiling reveals disease stage-dependent remodeling of mitochondrial and oxidative phosphorylation programs, with increased activity in prodromal disease followed by reduced activity in manifest PD, consistent with a transition in peripheral immune state during disease progression. High-resolution T cell analysis further identifies sex-dependent changes in cytotoxic CD8+ T-cell states and TCR clonal diversity. TCR motif analysis reveals disease-associated receptor groups with predicted specificities spanning PD-related, viral and autoimmune antigens. Together, these findings provide a comprehensive single-cell map of peripheral immune dysregulation in PD, defining dynamic and sex-dependent remodeling of peripheral immunity across the PD spectrum.",
  "abstract_shown": true,
  "affiliations": [
    "Icahn School of Medicine at Mount Sinai"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "name": "M. Rosen"
    },
    {
      "name": "J. O. Narcis Majos"
    },
    {
      "name": "D. Mattei"
    },
    {
      "name": "E. Mejia"
    },
    {
      "name": "C. Perez Mandry"
    },
    {
      "name": "B. Jang"
    },
    {
      "name": "K. BP"
    },
    {
      "name": "T. Naito"
    },
    {
      "name": "A. Allan"
    },
    {
      "name": "T. Khashan"
    },
    {
      "name": "C. Argyrou"
    },
    {
      "name": "M. Yang"
    },
    {
      "name": "D. Raymond"
    },
    {
      "name": "C. Young"
    },
    {
      "name": "K. Astudillo"
    },
    {
      "name": "A. Domingo"
    },
    {
      "name": "S. Frucht"
    },
    {
      "name": "S. Bressman"
    },
    {
      "name": "A. Tocheva"
    },
    {
      "name": "G. M. Riboldi"
    },
    {
      "name": "R. Saunders-Pullman"
    },
    {
      "affs": [
        0
      ],
      "name": "T. Raj"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8x9hpdn1gwwg3.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.23.26363800",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.23.26363800v1.full",
  "id": "8x9hpdn1gwwg3",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.23.26363800v1",
  "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": [
    [
      "medrxiv",
      "genetic and genomic medicine"
    ],
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7215063556",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.23.26363800v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/8x9hpdn1gwwg3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "10.64898/2026.09.23.26363800",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.23.26363800v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:genetic and genomic medicine",
      "subfield": "human-genetics"
    }
  ],
  "title": "Peripheral Immune Alterations and T Cell Clonal Dynamics Across the Parkinson's Disease Spectrum",
  "title_text": "Peripheral Immune Alterations and T Cell Clonal Dynamics Across the Parkinson's Disease Spectrum",
  "type": "preprint",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/8x9hpdn1gwwg3",
  "venue": "medRxiv",
  "versions": []
}