**5. ncRNA as a biomarker for disease**

#### **5.1 ncRNA biomarkers in Parkinson's disease**

A number of candidate miRNAs have been identified in plasma from PD patients by microarray, and validation in an independent cohort revealed the expression of miR-1826/miR-450b-3p, miR-626 and miR-505 were significantly different between control and PD subjects [136]. In a larger study, miRNAs known to be expressed in the CNS and involved in neuronal regulation were identified in the plasma of PD patients. The expression of miR-137 was increases and expression of miR-124 was decreased in PD patients compared with controls; however, there was no relation between these alterations and the severity of disease [137]. Using sequencing technologies a number of studies have identified miRNA candidates as biomarkers for PD. Subsequent validation by RT-PCR determined that miR-195 was increased and miR-185, miR-15b, miR-221, miR-181a, miR-141, miR-214, miR-146b-5p, miR-193-3p, miR-29c, miR-146a, miR-214 and miR-221 were decreased in PD patients [138–140]. Finally, one study identified differential expression of miR-1-3p, miR-22-5p and miR-29a-3p in the whole blood of PD patients using PCR [141]. It is important to note here that no miRNA has yet been identified as a biomarker for PD in two independent studies.

A number of independent studies have identified *Ang* variants in PD [78, 79], however the investigation of tsRNA as a biomarker for the disease is in its infancy. Using deep sequencing analysis of postmortem tissue Pantano et al. identified that tsRNA clusters can accurately differentiate between control, PD patients at premotor and motor stages of the disease [80]. Furthermore, in a small study sex-specific tsRNA differences were reported in the prefrontal cortex, cerebrospinal fluid and serum of PD patients [81].
