Peripheral Immune Alterations and T Cell Clonal Dynamics Across the Parkinson's Disease Spectrum

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.

Correlation of peripheral blood BMAL1 level with non-motor symptoms in Parkinson’s disease patients
Yanyan Jiang, Yufei Zhang, Luoqing Dong +1
Frontiers in neurology16 Oct 2026Peer-reviewedCC BYFull textNeurologyEurope PMC
Evaluation of peripheral and intranigral AAV-mediated Irisin delivery in a chronic AAV-A53T α-Synuclein overexpression mouse model of Parkinson’s disease
Chunyan Shu, Jiehong Huang, Wandi Pu +4
Frontiers in aging neuroscience16 Oct 2026Peer-reviewedCC BYFull textGeneral medicineEurope PMC
Peripheral Neuropathy in Parkinson’s Disease Treated with Device-Assisted Therapies: How Often It Is Reported Depends on How It Is Sought. A Systematic Review and Meta-Analysis
Natalia Blidaru, Delia Tulbă, Teodor Cristian Blidaru +5
Biomedicines1 Oct 2026Peer-reviewedCC BYFull textGeneral medicineEurope PMC
Inferior Frontal Gyrus Alterations in Freezing of Gait in Parkinson's Disease Without Evidence for Overall Hemispheric Lateralization: A Systematic Review and Activation Likelihood Estimation Meta-Analysis.
Seira Taniguchi, Hannah Deckmyn, Moran Gilat
The European journal of neuroscience29 Oct 2026Peer-reviewedCC BYFull textNeurologyEurope PMCPMC
Peripheral immunoinflammatory markers and clinical correlations in Parkinson's disease patients carrying LRRK2 G2385R and R1628P variants
H. X. Ding, T. S. Toh, N. J. Zulkefli +10
medRxiv20 Sep 2026PreprintCC BYFull textNeurologymedRxiv

Cite

BibTeX RIS

BibTeX

@misc{rosen2026peripheral,
  title = {{Peripheral Immune Alterations and T Cell Clonal Dynamics Across the Parkinson's Disease Spectrum}},
  author = {M. Rosen and J. O. Narcis Majos and D. Mattei and E. Mejia and C. Perez Mandry and B. Jang and K. BP and T. Naito and A. Allan and T. Khashan and C. Argyrou and M. Yang and D. Raymond and C. Young and K. Astudillo and A. Domingo and S. Frucht and S. Bressman and A. Tocheva and G. M. Riboldi and R. Saunders-Pullman and T. Raj},
  howpublished = {medRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.23.26363800},
  url = {https://www.medrxiv.org/content/10.64898/2026.09.23.26363800v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Peripheral Immune Alterations and T Cell Clonal Dynamics Across the Parkinson's Disease Spectrum
AU  - M. Rosen
AU  - J. O. Narcis Majos
AU  - D. Mattei
AU  - E. Mejia
AU  - C. Perez Mandry
AU  - B. Jang
AU  - K. BP
AU  - T. Naito
AU  - A. Allan
AU  - T. Khashan
AU  - C. Argyrou
AU  - M. Yang
AU  - D. Raymond
AU  - C. Young
AU  - K. Astudillo
AU  - A. Domingo
AU  - S. Frucht
AU  - S. Bressman
AU  - A. Tocheva
AU  - G. M. Riboldi
AU  - R. Saunders-Pullman
AU  - T. Raj
PY  - 2026
DA  - 2026/09/23
PB  - medRxiv
DO  - 10.64898/2026.09.23.26363800
UR  - https://www.medrxiv.org/content/10.64898/2026.09.23.26363800v1
AB  - 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.
ER  -

Abstract

Related

Cite