Plasma miRNA Biomarker Signatures in Parkinsonian Syndromes

Diagnosing atypical parkinsonian syndromes (APS) remains challenging due to overlapping clinical features and limited diagnostic tools. Brain-enriched microRNAs (miRNAs), which regulate neuronal development and function, are detectable in plasma and could serve as molecular biomarkers. This prospective study aimed to identify plasma brain-enriched miRNAs that can distinguish APS and elucidate affected molecular pathways. Reverse transcription-quantitative PCR (RT-qPCR) was performed on plasma samples from patients with idiopathic Parkinson's disease (iPD), multiple system atrophy (MSA), including the cerebellar subtype (MSA-C) and the parkinsonian subtype (MSA-P), progressive supranuclear palsy (PSP), and healthy controls. MiRNA expression analysis revealed distinct molecular fingerprints for each parkinsonian syndrome, with opposite trends between MSA and iPD compared to controls, suggesting distinct pathogenic mechanisms. Most dysregulated miRNAs clustered at chromosome (Chr)14q32 and shared binding sites for CREB1, CEBPB, and MAZ transcription factors. Pathway analysis revealed enrichment in prion diseases, Hippo signaling, TGF-beta signaling, and FoxO signaling pathways.