NeuralCipher Research overview
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Current clinical tests for Parkinson’s disease (PD) provide insufficient diagnostic accuracy leading to an urgent need for improved diagnostic biomarkers. MicroRNAs (miRNAs) are promising biomarkers of various diseases, including PD. This systematic review and meta-analysis aimed to pool all available data and assess the diagnostic accuracy of biofluid miRNAs in PD. All studies reporting data on miRNAs and their directions of change in PD patients compared to controls were included. Gene targets and significant pathways associated with miRNAs expressed in more than 3 biofluid studies with the same direction of change were analyzed using target prediction and enrichment analysis. A bivariate model was used to calculate sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio. While miR-24-3p and miR-214-3p were the most reported miRNA in different studies (7 each), miR-331-5p was found to be consistently up regulated in 4 different sources of biofluid. Importantly, miR-19b-3p, miR-24-3p, miR-146a-5p, and miR-221-3p were identified to be reported without conflicting directions of change in the same biofluid type (serum) in multiple studies and bioinformatic analysis found the targets of these miRNAs to be associated with pathways important in PD pathology. Of the 102 studies from the systematic review, 17 were meta-analyzed. Meta-analysis showed that biofluid miRNAs can discriminate between PD patients and controls with good sensitivity (0.82, 95% CI 0.76–0.87) and specificity (0.80, 95% CI 0.74–0.84) with an AUC of 0.87 (95% CI 0.83–0.89). But we found multiple studies failed to match the sex ratios in their groups therefore possibly introducing a selection bias where overall more males with PD were studied than any other group. Overall, our study captures key miRNAs which may represent a point of focus for future studies and the development of diagnostic panels whilst also highlighting the importance of appropriate study design to develop representative biomarker panels for the diagnosis of PD.
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