Objective: To identify plasma-derived microRNAs (miRNAs) to serve as potential diagnostic and prognostic biomarkers of Parkinson’s disease (PD).

Background: PD is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Current clinical tests for PD provide insufficient diagnostic accuracy leading to an urgent need for biomarkers. MiRNAs are small non-coding RNAs which participate in post-transcriptional control of gene expression. The utility of miRNAs as biomarkers lie in their stability and ease of measurement within various biofluids, including plasma.

Method: PD patients (n=35) and age and sex-matched controls (n=34) were recruited from Dunedin, New Zealand. A subgroup of patients (n=26) were reassessed longitudinally after 4 years. The following data were obtained: Unified Parkinson’s Disease Rating Scale, Montreal Cognitive Assessment, demographics, sleep quality, anxiety, depression, and dyskinesia severity. Fasting blood was collected at baseline and at 4-years. RNA was isolated from EDTA-plasma (mirVANA PARIS). Neuropathology-related miRNAs (n=187) were measured using custom-designed low-density TaqMan arrays. Data were normalized using R version 3.4.3 (library HTqPCR, normrank). Differentially expressed miRNAs were identified using the ∆∆Ct method and the Mann-Whitney-U test for significance (Benjamini-Hochberg, p<0.05).

Results: We found 12 differentially expressed miRNAs in PD patients compared to controls (adjusted p<0.05) [9 upregulated (fold change: 1.31–1.73), 3 downregulated (fold change: 0.68–0.82)]. In the longitudinal assessment of patients, 13 miRNAs were differentially expressed (adjusted p<0.05) [6 upregulated (fold change: 1.30–1.80), 7 downregulated (fold change: 0.59–0.86)]. One miRNA was common between the analyses, although the direction of change was incongruent (up in PD vs control; down in longitudinal PD), supporting the importance of further investigation into the interaction of this miRNA with underlying pathology.

Conclusion: Our results suggest that specific groups of miRNAs are altered at different stages of PD and could serve as biomarkers of diagnosis and disease progression. Early diagnosis is crucial for the development of breakthrough therapies, introduction of preventative treatments and improvement of patients’ quality of life. Further investigation of these miRNAs and their downstream targets will enable a better understanding of the underlying pathology associated with PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/microrna-expression-in-the-diagnosis-of-parkinsons-disease/