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, Alessandro Sette*

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Article number1875
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease'. Together they form a unique fingerprint.

  • Cite this

    Lindestam Arlehamn, C. S., Dhanwani, R., Pham, J., Kuan, R., Frazier, A., Rezende Dutra, J., Phillips, E., Mallal, S., Roederer, M., Marder, K. S., Amara, A. W., Standaert, D. G., Goldman, J. G., Litvan, I., Peters, B., Sulzer, D., & Sette, A. (2020). α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease. Nature communications, 11(1), [1875]. https://doi.org/10.1038/s41467-020-15626-w