{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:40:59Z","timestamp":1792464059207,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,29]]},"group-title":"Genetic and Genomic Medicine","reference-count":90,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>The role of peripheral immunity in Parkinson\u2019s 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.<\/jats:p>","DOI":"10.64898\/2026.09.23.26363800","type":"posted-content","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:45:18Z","timestamp":1790909118000},"source":"Crossref","is-referenced-by-count":0,"title":["Peripheral Immune Alterations and T Cell Clonal Dynamics Across the Parkinson\u2019s Disease Spectrum"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5941-8485","authenticated-orcid":false,"given":"Mikaela","family":"Rosen","sequence":"first","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Nash Family Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Ronald M. Loeb Center for Alzheimer\u2019s Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Oriol Narcis","family":"Majos","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Nash Family Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Ronald M. Loeb Center for Alzheimer\u2019s Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6221-9321","authenticated-orcid":false,"given":"Daniele","family":"Mattei","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Nash Family Department of Neuroscience & Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA"},{"name":"Ronald M. 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