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There is a high misdiagnosis rate between Parkinson’s disease (PD) and atypical parkinsonian disorders (APD), such as progressive supranuclear palsy (PSP), the second most common parkinsonian syndrome. In our earlier studies, we identified and replicated RNA blood biomarkers in several independent cohorts, however, replication in a cohort that includes PSP patients has not yet been performed. To this end, we evaluated the diagnostic potential of nine previously identified RNA biomarkers using quantitative PCR assays in 138 blood samples at baseline from PD, PSP and healthy controls (HCs) nested in the PD Biomarkers Program. Linear discriminant analysis showed that  COPZ1  and  PTPN1  distinguished PD from PSP patients with 62.5% accuracy. Five biomarkers,  PTPN1 ,  COPZ1 ,  FAXDC2 ,  SLC14A1s  and  NAMPT  were useful for distinguishing PSP from controls with 69% accuracy. Several biomarkers correlated with clinical features in PD patients.  SLC14A1-s  correlated with Unified Parkinson’s Disease Rating Scale total and part III scores. In addition,  COPZ1 ,  PTPN1  and  MLST8 , correlated with Montreal Cognitive Assessment (MoCA). Interestingly,  COPZ1 ,  EFTUD2  and  PTPN1  were downregulated in cognitively impaired (CI) compared to normal subjects. Linear discriminant analysis showed that age,  PTPN1 ,  COPZ1 ,  FAXDC2 ,  EFTUD2  and  MLST8  distinguished CI from normal subjects with 65.9% accuracy. These results suggest that  COPZ1  and  PTPN1  are useful for distinguishing PD from PSP patients. In addition, the combination of  PTPN1 ,  COPZ1 ,  FAXDC2 ,  EFTUD2  and  MLST8  is a useful signature for cognitive impairment. Evaluation of these biomarkers in a larger study will be a key to advancing these biomarkers into the clinic.

Evaluation of RNA Blood Biomarkers in the Parkinson’s Disease Biomarkers Program