Objective: This study explored the potential use of alpha-synuclein (α-syn) in plasma neuronal exosomes as a biomarker for early Parkinson’s disease (PD) diagnosis and disease progression.

Background: The identification of reliable diagnostic and prognostic biomarkers for PD is urgently needed. α-syn, the signature protein in PD, could be transported from the central nervous system into the peripheral blood via neuronal exosomes.

Method: 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). Neuronal exosomes were isolated from plasma by an immunoprecipitation procedure using antibodies against neuronal cell adhesion molecule (L1CAM). α-syn levels were measured by electrochemiluminescence (ECL) 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: α-syn levels in plasma neuronal exosomes were significantly higher in early stage PD patients compared with HCs (p=0.007). Differences in α-syn levels between iRBD patients and HCs did not reach statistical significance (p=0.08). In addition, Spearman correlation analysis revealed neuronal exosomal α-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 α-syn rather than baseline α-syn levels were associated with higher risk for motor symptom progression in PD (p = 0.039).

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

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-longitudinal-study-on-alpha-synuclein-in-plasma-neuronal-exosomes-as-a-biomarker-for-parkinsons-disease-development-and-progression/