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 a-synuclein (a-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). a-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 a-syn levels in plasma neuronal exosomes were significantly higher in patients with early-stage PD compared with HCs (P = 0.007). Differences in a-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 a-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 earlystage PD, a Cox regression analysis adjusted for age and gender showed that longitudinally increased a-syn rather than baseline a-syn levels were associated with higher risk for motor symptom progression in PD (P = 0.039). Conclusions: Our results suggested that a-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.

Recent Advances on Extracellular Vesicles in Central Nervous System Diseases

“…Similar phenomenon was observed that patients whose α-syn longitudinally increased underwent deterioration of motor symptom in the follow-up. 66 Some other studies confirmed the value of increased exosomal αsyn, oligomeric α-syn or the ratio of it to total α-syn in different biological fluids as biomarkers of PD. [67][68][69] Interestingly, Si et al reported α-syn level in CNSderived exosomes is lower in PD patients than essential tremor and healthy groups.…”

A modern view on potential biomarkers of Parkinson’s disease (review)

“…In addition, Spearman's correlation analysis revealed that neuronal exosomal α-synuclein concentrations were correlated with Movement Disorders Society UPDRS III/(I + II + III) scores, Non-Motor Symptom Questionnaire scores and Sniffin' Sticks 16-item test scores of patients with PD. 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-synuclein rather than baseline α-synuclein levels were associated with higher risk for motor symptom progression in PD [37].…”

Glia-Derived Extracellular Vesicles in Parkinson’s Disease

“…Importantly, it has to be taken into account that the outcome depends from the source of the EVs carrying α-Syn, which can be plasma, serum or CSF. In fact, α-Syn detected in plasma deriving EVs may be also be produced by plasma cells [184,185].…”