Abstract

BackgroundBlood-based test for predicting disease progression and early diagnosis of Parkinson’s disease (PD) is an unmet need in the clinic. The profiles of microRNAs (miRNAs) are regarded as potential diagnostic biomarkers for human diseases, whereas miRNAs in the periphery are susceptible to the influence of various components. MiRNAs enriched in serum extracellular vesicles (EVs) have demonstrated disease-specific advantages in diagnosis due to their high abundance, stability and resistance to degradation. This study was aimed to screen differentially expressed EV-derived miRNAs between healthy controls and PD patients to aid in diagnosis of PD.MethodsA total of 31 healthy controls and 72 patients with a diagnosis of PD at different Hoehn and Yahr stages in Tangdu Hospital were included. In total, 185 differentially expressed miRNAs were obtained through RNA sequencing of serum EVs as well as edgeR and t-test analyses. Subsequently, the weighted gene co-expression network analysis (WGCNA) was utilized to identify the commonly expressed miRNAs in all stages of PD by constructing connections between modules, and specifically expressed miRNAs in each stage of PD by functional enrichment analysis. After aligning these miRNAs with PD-related miRNAs in Human miRNA Disease Database, the screened miRNAs were further validated by receiver operating characteristic (ROC) curves and quantitative real-time polymerase chain reaction (qRT-PCR) using peripheral blood EVs from 40 more participants.ResultsWGCNA showed that 4 miRNAs were commonly associated with all stages of PD and 13 miRNAs were specifically associated with different stages of PD. Of the 17 obtained miRNAs, 7 were validated by ROC curve analysis and 7 were verified in 40 more participants by qRT-PCR. Six miRNAs were verified by both methods, which included 2 miRNAs that were commonly expressed in all stages of PD and 4 miRNAs that were specifically expressed in different stages of PD.ConclusionsThe 6 serum EV-derived miRNAs, hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-199a-3p, hsa-miR-28-5p, hsa-miR-22-5p and hsa-miR-151a-5p, may potentially be used as biomarkers for PD progression and for early diagnosis of PD in populations.

Highlights

  • Blood-based test for predicting disease progression and early diagnosis of Parkinson’s disease (PD) is an unmet need in the clinic

  • The presence of extracellular vesicles (EVs) was verified by western blot using antibodies for CD63, TSG101 and CD81, with cell-related marker (GAPDH) as a control for extracted vesicles (Fig. 1a)

  • The expression levels of miR-153 and miR-223 are significantly downregulated in the saliva of PD individuals, and their upstream heme oxygenase-1 in EVs could be transported from the central nervous system (CNS) to the peripheral biofluids, all of them may be potential biomarkers for early PD [35, 36]

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Summary

Introduction

Blood-based test for predicting disease progression and early diagnosis of Parkinson’s disease (PD) is an unmet need in the clinic. Compared to the complication of DaTSCAN and invasive nature of CSF extraction, the blood-based test is rapid and safe, having potentials for use to detect biomarkers [5]. Apart from neurofilament light chain (NFL) which has been recognized as a marker for axon injury and may have been shown to be able to distinguish PD from atypical parkinsonian disorders (APDs) that show similar clinical symptoms with early PD [6], there are few validated biomarkers for screening PD in early stage and monitoring disease progression [7]. The expression profile of miRNAs in the extracellular environment can reflect a pathological state [10], having higher diagnostic potential for NDDs

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