The study reports consistent up-regulation of tRNA-derived miR-1274b in tear fluid from small PD cohorts, with in-silico predicted targets and network links to synaptic regulation and PD-related genes.

Identifies a non-invasive biomarker candidate that could aid diagnosis or stratification, though small sample sizes and no functional validation limit immediate therapeutic or mechanistic utility.

BACKGROUND: Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by motor and non-motor symptoms. Early diagnosis remains challenging due to the lack of reliable, non-invasive biomarkers. Here, we explored the potential of tear fluid (TF) as a diagnostic source by profiling its microRNA (miRNA) content. METHODS: The study included a discovery (8 PD, 7 healthy controls (HC)) and a replication cohort (9 PD, 9 HC). miRNA expression was assessed using TaqMan Human MicroRNA arrays. Independent in-silico validation was conducted using a qPCR-based miRNA array dataset comprising pooled cDNA samples from controls (n = 10) and PD patients (n = 29). The relationship between microRNA expression and composite clinical scores in PD patients was explored. Target gene prediction, pathway enrichment, and interaction network analyses were performed. RESULTS: The t-RNA-derived miR-1274b was consistently upregulated in the TF of PD patients across the discovery and replication cohorts, with additional in-silico support from the independent dataset. Increased expression was particularly evident in a PD subgroup characterized by combined non-motor autonomic symptoms. Predicted target genes were associated with neurodegeneration and cellular dysfunction. Over-representation analysis highlighted pathways related to negative regulation of synaptic transmission, while network analysis revealed interactions between miRNA targets and key PD-related genes, supporting a potential role in disease mechanisms. CONCLUSIONS: Our findings identify miR-1274b as a TF-based miRNA associated with PD, supporting its potential as a non-invasive biomarker. Further studies with larger cohorts and other neurodegenerative diseases are needed to validate these results and explore their clinical applicability.