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

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, David G. Standaert, Jennifer G. Goldman, Irene Litvan, Bjoern Peters, David Sulzer () and Alessandro Sette ()
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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
Simon Mallal: Vanderbilt University School of Medicine
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
David Sulzer: Columbia University
Alessandro Sette: Division of Vaccine Discovery, La Jolla Institute for Immunology

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-15626-w

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