Plasma acellular transcriptome contains Parkinson’s disease signatures that can inform clinical diagnosis

We aimed to identify plasma cell-free transcripts (cfRNA) associated with Parkinson’s disease (PD) that also have a high predictive value to differentiate PD from healthy controls. Leveraging two independent populations from two different movement disorder centers we identified 2,188 differentially expressed cfRNAs after meta-analysis. The identified transcripts were enriched in PD relevant pathways, such as PD (p=9.26×10 ^-4 ), ubiquitin-mediated proteolysis (p=7.41×10 ^-5 ) and endocytosis (p=4.21×10 ^-6 ). Utilizing in-house and publicly available brain, whole blood, and acellular plasma transcriptomic and proteomic PD datasets, we found significant overlap across dysregulated biological species in the different tissues and the different biological layers. We developed three predictive models containing increasing number of transcripts that can distinguish PD from healthy control with an area under the ROC Curve (AUC) ≥0.85. Finally, we showed that several of the predictive transcripts significantly correlate with symptom severity measured by UPDRS-III. Overall, we have demonstrated that cfRNA contains pathological signatures and has the potential to be utilized as biomarker to aid in PD diagnostics and monitoring.