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

2020; Nature Portfolio; Volume: 11; Issue: 1 Linguagem: Inglês

10.1038/s41467-020-15626-w

2041-1723

Cecilia S. Lindestam Arlehamn, Rekha Dhanwani, John Pham, Rebecca Kuan, April Frazier, Juliana Rezende Dutra, Elizabeth J. Phillips, S. Mallal, Mario Roederer, Karen Marder, Amy W. Amara, David G. Standaert, Jennifer G. Goldman, Irene Litvan, Bjoern Peters, David Sulzer, Alessandro Sette,

Amyotrophic Lateral Sclerosis Research

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.