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Circulating Brain‐Enriched MicroRNAs for Detection and Discrimination of Idiopathic and Genetic Parkinson's Disease

Ravanidis, Stylianos, Bougea, Anastasia, Papagiannakis, Nikolaos, Maniati, Matina, Koros, Christos, Simitsi, Athina‐Maria, Bozi, Maria, Pachi, Ioanna, Stamelou, Maria, Paraskevas, George P., Kapaki, Elisabeth, Moraitou, Marina, Michelakakis, Helen, Stefanis, Leonidas, Doxakis, Epaminondas·2020·Movement Disorders
DOI 10.1002/mds.27928
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Abstract

Background: A minimally invasive test for early detection and monitoring of Parkinson's disease (PD) is a highly unmet need for drug development and planning of patient care. Blood plasma represents an attractive source of biomarkers. MicroRNAs (miRNAs) are conserved noncoding RNA molecules that serve as posttranscriptional regulators of gene expression. As opposed to ubiquitously expressed miRNAs that control house‐keeping processes, brain‐enriched miRNAs regulate diverse aspects of neuron development and function. These include neuron‐subtype specification, axonal growth, dendritic morphogenesis, and spine density. Backed by a large number of studies, we now know that the differential expression of neuron‐enriched miRNAs leads to brain dysfunction. Objectives: The aim was to identify subsets of brain‐enriched miRNAs with diagnostic potential for familial and idiopathic PD as well as specify the molecular pathways deregulated in PD. Methods: Initially, brain‐enriched miRNAs were selected based on literature review and validation studies in human tissues. Subsequently, real‐time reverse transcription polymerase chain reaction was performed in the plasma of 100 healthy controls and 99 idiopathic and 53 genetic (26 alpha‐synuclein A53T and 27 glucocerebrosidase) patients. Statistical and bioinformatics analyses were carried out to pinpoint the diagnostic biomarkers and deregulated pathways, respectively. Results: An explicit molecular fingerprint for each of the 3 PD cohorts was generated. Although the idiopathic PD fingerprint was different from that of genetic PD, the molecular pathways deregulated converged between all PD subtypes. Conclusions: The study provides a group of brain‐enriched miRNAs that may be used for the detection and differentiation of PD subtypes. It has also identified the molecular pathways deregulated in PD. © 2019 International Parkinson and Movement Disorder Society

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  • Stable reference (miR-103a-3p, miR-191-5p, miR-425-5p, miR-223-3p, miR-423-3p) and hemolysis (miR-23a, miR-451a) miRNA controls were included in the plasma analysis.

    “Stable reference (miR‐103a‐3p, miR‐191‐5p, miR‐425‐5p, miR‐223‐3p, miR‐423‐3p) and hemolysis (miR‐23a, miR‐451a) miRNA controls were included in the plasma analysis and were identical to previous study. 14”

    From Validation of differentially expressed brain‐enriched microRNAs in the plasma of PD patients (2020) · cites this paper as [14]

  • Previously, eight brain-enriched miRNAs were found to be differentially expressed between healthy controls and PD patients: miR-7-5p, miR-22-3p, miR-124-3p, miR-136-3p, miR-139-5p, miR-330-5p, miR-433-3p, and miR-495-3p.

    “Previously, eight brain‐enriched miRNAs were found to be differentially expressed between healthy controls and PD patients. 14 These were miR‐7‐5p, miR‐22‐3p, miR‐124‐3p, miR‐136‐3p, miR‐139‐5p, miR‐330‐5p, miR‐433‐3p, and miR‐495‐3p.”

    From Validation of differentially expressed brain‐enriched microRNAs in the plasma of PD patients (2020) · cites this paper as [14]

  • Brain-enriched miRNAs can differentiate healthy controls from genetic and idiopathic PD subjects.

    “We previously reported that brain‐enriched miRNAs can differentiate healthy controls from genetic and idiopathic PD subjects. 14”

    From Validation of differentially expressed brain‐enriched microRNAs in the plasma of PD patients (2020) · cites this paper as [14]

  • Four miRNAs (miR-132-3p, miR-154-5p, miR-323a-3p, miR-409-3p) differed marginally non-significantly between the two groups in the previous study.

    “Four miRNAs that were found to differ in their expression between the two groups, but in a marginal non‐significant manner, were also included in the analysis. These were miR‐132‐3p (P = 0.12), miR‐154‐5p (P = 0.09), miR‐323a‐3p (P = 0.13), and miR‐409‐3p (P = 0.10).”

    From Validation of differentially expressed brain‐enriched microRNAs in the plasma of PD patients (2020) · cites this paper as [14]

  • The previous findings on brain-derived miRNAs were validated using an independent idiopathic PD cohort.

    “Here, we established the validity of our previous findings which had a specific focus on brain‐derived miRNAs, 14 using an independent idiopathic PD cohort, and in‐depth analyzed current and previous data together to reveal not only a panel of deregulated miRNAs but also the upstream and downstream mediators of their effect.”

    From Validation of differentially expressed brain‐enriched microRNAs in the plasma of PD patients (2020) · cites this paper as [14]

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Metadata

Authors
Ravanidis, S., Bougea, A., Papagiannakis, N., Maniati, M., Koros, C., Simitsi, A., Bozi, M., Pachi, I., Stamelou, M., Paraskevas, G. P., Kapaki, E., Moraitou, M., Michelakakis, H., Stefanis, L., & Doxakis, E.
Affiliations
  • Center of Basic Research, Biomedical Research Foundation Academy of Athens Athens Greece
  • Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens Athens Greece
  • 1st Department of Neurology National and Kapodistrian University of Athens Medical School, Eginition Hospital, Athens Greece
  • 2nd Department of Neurology National and Kapodistrian University of Athens Medical School Athens Greece
  • Department of Enzymology and Cellular Function Institute of Child Health Athens Greece
ORCID
Venue
Movement Disorders
Publisher
Wiley
Published
2019-12-04
Volume
35
Issue
3
Pages
457-467
ISSN
  • 0885-3185
  • 1531-8257
DOI
10.1002/mds.27928
Cited by
51
References
8
Language
en
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Funders
Michael J. Fox Foundation for Parkinson's Research (13353)

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