Cerebrospinal fluid-driven extracellular vesicle as a potential diagnostic biomarker for multiple system atrophy

Given that Parkinsonian disorders, including Parkinson's disease (PD) and multiple system atrophy-parkinsonism (MSA-P), often have similar clinical presentations, making a clinical diagnosis can be challenging. In the present study, we extracted and analyzed extracellular vesicles (EVs) from the cerebrospinal fluid of individuals diagnosed with PD (N = 16), MSA-P (N = 16), and amyotrophic lateral sclerosis (ALS) (N = 16), with the latter serving as the control group. Transcriptomic analysis identified 7426 and 8003 differentially expressed RNAs between MSA and ALS, and MSA and PD, respectively. Four transcripts (RN7SL3, RN7SL1, MIR19B2, and SYF2P2) were among the top six transcripts upregulated in MSA-P compared with both ALS and PD. Proteomic analysis revealed notable changes in the levels of corneodesmosin, psoriasin (S100A7), and dystroglycan1 in MSA-P compared with ALS and PD. Notably, S100A7 mRNA levels were also significantly lower in MSA than in the other diseases examined. Furthermore, we found a positive correlation between S100A7 mRNA levels and the heart mean/mediastinum mean ratio on ¹²³I-metaiodobenzylguanidine myocardial scintigraphy, whereas SYF2P2 mRNA levels were negatively correlated with both the asymmetry index on dopamine transporter scans and Mini Mental State Examination scores. A positive correlation was found between S100A7 levels and motor symptoms. In distinguishing MSA-P from PD, MIR19B2 exhibited the highest Area Under Curve (AUC) of 0.867, demonstrating 100 % sensitivity and 68.7 % specificity. Conversely, the results for CDSN showed an AUC value of 0.847, with 58.3 % sensitivity and 100 % specificity. These combined transcriptomic and proteomic biomarkers could serve as valuable diagnostic tools for MSA.