A longitudinal study on α-synuclein in plasma neuronal exosomes as a biomarker for Parkinson's disease development and progression

Abstract

Background and purpose: The identification of reliable diagnostic and prognostic biomarkers for Parkinson's disease (PD) is urgently needed. Here, we explored the potential use of α-synuclein (α-syn) in plasma neuronal exosomes as a biomarker for early PD diagnosis and disease progression.

Methods: This study included both cross-sectional and longitudinal designs. The subjects included 36 patients with early-stage PD, 17 patients with advanced PD, 20 patients with idiopathic rapid eye movement sleep behavior disorder and 21 healthy controls (HCs). α-syn levels were measured by electrochemiluminescence immunoassay. A subgroup of patients with early-stage PD (n = 18) participated in a follow-up examination with repeated blood collection and clinical assessments after an average of 22 months.

Results: The α-syn levels in plasma neuronal exosomes were significantly higher in patients with early-stage PD compared with HCs (P = 0.007). Differences in α-syn levels between patients with idiopathic rapid eye movement sleep behavior disorder and HCs did not reach statistical significance (P = 0.08). In addition, Spearman correlation analysis revealed that neuronal exosomal α-syn concentrations were correlated with Movement Disorders Society Unified Parkinson's Disease Rating Scale III/(I + II + III) scores, Non-Motor Symptom Questionnaire scores and Sniffin' Sticks 16-item test scores of patients with PD (P < 0.05). After a mean follow-up of 22 months in patients with early-stage PD, a Cox regression analysis adjusted for age and gender showed that longitudinally increased α-syn rather than baseline α-syn levels were associated with higher risk for motor symptom progression in PD (P = 0.039).

Conclusions: Our results suggested that α-syn in plasma neuronal exosomes may serve as a biomarker to aid early diagnosis of PD and also as a prognostic marker for PD progression.

Keywords: Parkinson's disease; biomarker; diagnosis; disease progression; idiopathic rapid eye movement sleep behavior disorder; neuronal exosome; plasma; α-synuclein.