Objective: The aims were to (1) explore the concentration differences of α-syn species in different blood components between PD and healthy controls (HC), and between PD and atypical parkinsonian syndromes (APS) and (2) investigate the diagnostic performance of blood α-syn species in the diagnosis of PD.

Background: α-Synuclein (α-syn) is a major pathological hallmark of Parkinson’s disease (PD). The diagnostic utility of blood α-syn is still under investigation in PD.

Method: We searched PubMed, Embase, Web of Science, and Cochrane Library up to September 18, 2022 for original studies reporting total, oligomeric, phosphorylated, or other posttranslational modified α-syn concentrations in different blood components between PD and HC, and between PD and APS. Standardized mean differences (SMDs) were calculated using random-effects model and heterogeneity was reported as I2. Subgroup analyses and meta-regression analyses were performed to explore the source of heterogeneity. The pooled sensitivity, specificity, and the diagnostic odds ratio (DOR) were calculated using a hierarchical summary receiver operating characteristic model. Network meta-analysis (NMA) was performed using ANOVA model. Quality assessment was assessed using the QUADAS-2 tool.

Results: Seventy-eight articles were included in this systematic review and 63 articles were selected for the meta-analysis. Red blood cell (RBC) oligomeric α-syn (o-α-syn) (SMD, 0.99; 95%CI, 0.80-1.18; I2=0%), serum total α-syn (t-α-syn) (SMD, 0.85; 95%CI, 0.17-1.53; I2=94%), and plasma neuron-derived exosomal (NDE) α-syn (SMD, 0.54; 95%CI, 0.16-0.91; I2=82%) were significantly increased in PD compared to HC. Other blood α-syn biomarkers showed non-significant results. Sensitivity and specificity for distinguishing PD and HC were: 0.75 and 0.66, respectively for plasma NDE α-syn; 0.74 and 0.67, respectively for serum t-α-syn; and 0.79 and 0.75 for RBC o-α-syn. NMA indicated that RBC o-α-syn (DOR, 11.19; 95%CI, 0.84-45.74) might have higher diagnostic accuracy than serum t-α-syn (DOR, 7.78; 95%CI, 2.05-19.84) and NDE α-syn (DOR, 5.07; 95%CI, 1.14-13.67).

Conclusion: Although RBC o-α-syn, serum t-α-syn, and plasma NDE α-syn might aid PD diagnosis, the diagnostic performance of α-syn species in different blood components is still suboptimal.

References: 1. Niu M, Li Y, Li G, et al. A longitudinal study on α-synuclein in plasma neuronal exosomes as a biomarker for Parkinson’s disease development and progression. Eur J Neurol. 2020;27(6):967-974. doi.10.1111/ene.14208
2. Stuendl A, Kraus T, Chatterjee M, et al. α-Synuclein in Plasma-Derived Extracellular Vesicles Is a Potential Biomarker of Parkinson’s Disease. Mov Disord. 2021;36(11):2508-2518. doi.10.1002/mds.28639

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MDS Abstracts - https://www.mdsabstracts.org/abstract/diagnostic-utility-of-blood-%ce%b1-synuclein-in-parkinsons-disease-a-systematic-review-and-meta-analysis/