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α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease

Author

Listed:
  • Cecilia S. Lindestam Arlehamn

    (Division of Vaccine Discovery, La Jolla Institute for Immunology)

  • Rekha Dhanwani

    (Division of Vaccine Discovery, La Jolla Institute for Immunology)

  • John Pham

    (Division of Vaccine Discovery, La Jolla Institute for Immunology)

  • Rebecca Kuan

    (Division of Vaccine Discovery, La Jolla Institute for Immunology)

  • April Frazier

    (Division of Vaccine Discovery, La Jolla Institute for Immunology)

  • Juliana Rezende Dutra

    (Columbia University Medical Center)

  • Elizabeth Phillips

    (Vanderbilt University School of Medicine
    Murdoch University)

  • Simon Mallal

    (Vanderbilt University School of Medicine
    Murdoch University)

  • Mario Roederer

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Karen S. Marder

    (Columbia University Medical Center)

  • Amy W. Amara

    (University of Alabama at Birmingham)

  • David G. Standaert

    (University of Alabama at Birmingham)

  • Jennifer G. Goldman

    (Shirley Ryan AbilityLab, Northwestern University Feinberg School of Medicine)

  • Irene Litvan

    (University of California San Diego)

  • Bjoern Peters

    (Division of Vaccine Discovery, La Jolla Institute for Immunology
    University of California San Diego)

  • David Sulzer

    (Columbia University
    Columbia University
    New York State Psychiatric Institute)

  • Alessandro Sette

    (Division of Vaccine Discovery, La Jolla Institute for Immunology
    University of California San Diego)

Abstract

A diagnosis of motor Parkinson’s disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between α-synuclein (α-syn) T cell reactivity and PD. A longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis.

Suggested Citation

  • Cecilia S. Lindestam Arlehamn & Rekha Dhanwani & John Pham & Rebecca Kuan & April Frazier & Juliana Rezende Dutra & Elizabeth Phillips & Simon Mallal & Mario Roederer & Karen S. Marder & Amy W. Amara , 2020. "α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15626-w
    DOI: 10.1038/s41467-020-15626-w
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    Cited by:

    1. Simone Bido & Sharon Muggeo & Luca Massimino & Matteo Jacopo Marzi & Serena Gea Giannelli & Elena Melacini & Melania Nannoni & Diana Gambarè & Edoardo Bellini & Gabriele Ordazzo & Greta Rossi & Camill, 2021. "Microglia-specific overexpression of α-synuclein leads to severe dopaminergic neurodegeneration by phagocytic exhaustion and oxidative toxicity," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

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