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

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 alpha-synuclein (alpha-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 early stage PD patients, 17 advanced PD patients, 20 idiopathic REM sleep behavior disorder (iRBD) patients and 21 healthy controls (HCs). alpha-syn levels were measured by electrochemiluminescence immunoassay. A subgroup of early stage PD patients (n=18) participated in a follow-up examination with repeated blood collection and clinical assessments after an average of 22 months. RESULTS: alpha-syn levels in plasma neuronal exosomes were significantly higher in early stage PD patients compared with HCs (p=0.007). Differences in alpha-syn levels between iRBD patients and HCs did not reach statistical significance (p=0.08). In addition, Spearman correlation analysis revealed neuronal exosomal alpha-syn concentrations were correlated with UPDRS III/ (I+II+III) scores, NMSQ scores and SS-16 scores of patients with PD (p<0.05). After a mean follow-up of 22 months in early stage PD patients, a Cox regression analysis adjusted for age and gender showed that longitudinally increased alpha-syn rather than baseline alpha-syn levels were associated with higher risk for motor symptom progression in PD (p = 0.039). CONCLUSIONS: Our results suggested that alpha-syn in plasma neuronal exosomes may serve as a biomarker to aid early diagnosis of PD, and also a prognostic marker for PD progression.