NeuralCipher Research overview
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AbstractNeurodegeneration in Parkinson’s disease (PD) precedes diagnosis by years. Early neurodegeneration may be reflected in RNA levels and measurable as a biomarker. Here, we present the largest quantification of whole blood linear and circular RNAs (circRNA) in early-stage PD, using RNA sequencing data from two cohorts (PPMI = 259 PD, 161 Controls; ICICLE-PD = 48 PD, 48 Controls). We identified a replicable increase inTMEM252andLMNB1gene expression in PD. We identified novel differences in the expression of circRNAs fromESYT2,BMS1P1andCCDC9, and replicated trends of previously reported circRNAs. Overall, using circRNA as a diagnostic biomarker in Parkinson’s did not show any clear improvement over linear RNA. More interestingly, we observed a general reduction in circRNA expression in both PD cohorts, accompanied by an increase inRNASELexpression. This imbalance implicates the activation of an innate antiviral immune response and suggests a previously unknown aspect of circRNA regulation in PD.
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