Potential of non-coding RNA as biomarkers for progressive supranuclear palsy.

Objective markers for the neurodegenerative disorder progressive supranuclear palsy (PSP) are needed to help provide a timely diagnosis with certainty. Non-coding RNA (ncRNA), including microRNA, piwi-RNA, and transfer RNA, shown to be good candidates for markers in other neurodegenerative disease, but this had not been investigated in PSP. Therefore, as proof of principle, we sought to identify whether they were dysregulated in the matched serum and CSF of PSP patients (n=31) compared to healthy controls (n=20). Using RNA-sequencing, we found a number of ncRNA that showed dysregulation. Using reverse transcription-quantitative PCR, we found in serum significant down-regulation in hsa-miR-92a-3p, hsa-miR-626, hsa-piR-31068, and tRNA-ValCAC. In CSF, both hsa-let-7a-5p and hsa-piR-31068 showed significant up-regulation, consistent with their changes observed in the RNA-seq results. Interestingly, we saw no correlation in the expression of hsa-piR-31068 within our matched serum and CSF samples, suggesting there is no common mechanism between the two biofluids causing this dysregulation. While these changes were in a small cohort of samples, we have provided for the first time evidence that ncRNA in biofluids could be possible diagnostic biomarkers for PSP and further work will help to expand this potential.