Identification of blood serum micro-RNAs associated with idiopathic and LRRK2 Parkinson's disease

Authors

  • Teresa Botta-Orfila,

    1. Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Centro de Investigación sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • Xavier Morató,

    1. Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Centro de Investigación sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • Yaroslau Compta,

    1. Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Centro de Investigación sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain
    2. Movement Disorders Unit, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • Juan José Lozano,

    1. Bioinformatics Platform, Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas (CIBEREHD)-Centre Esther Koplovitz (CEK), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • Neus Falgàs,

    1. Movement Disorders Unit, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • Francesc Valldeoriola,

    1. Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Centro de Investigación sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain
    2. Movement Disorders Unit, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • Claustre Pont-Sunyer,

    1. Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Centro de Investigación sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain
    2. Movement Disorders Unit, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • Dolores Vilas,

    1. Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Centro de Investigación sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain
    2. Movement Disorders Unit, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • Lourdes Mengual,

    1. Laboratory and Department of Urology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • Manel Fernández,

    1. Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Centro de Investigación sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • José Luis Molinuevo,

    1. Movement Disorders Unit, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Catalonia, Spain
    2. Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • Anna Antonell,

    1. Movement Disorders Unit, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Catalonia, Spain
    2. Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • Maria José Martí,

    1. Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Centro de Investigación sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain
    2. Movement Disorders Unit, Department of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • Rubén Fernández-Santiago,

    1. Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Centro de Investigación sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain
    Search for more papers by this author
  • Mario Ezquerra

    Corresponding author
    1. Laboratory of Neurodegenerative Disorders, Department of Neurology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)-Centro de Investigación sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Catalonia, Spain
    • Correspondence to: Mario Ezquerra, PhD, Parkinson's Disease and Movement Disorders Unit, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación sobre Enfermedades Neurodegenerativas (CIBERNED), 08036 Barcelona, Spain. E-mail: ezquerra@clinic.ub.es

    Search for more papers by this author

Abstract

Blood-cell-free circulating micro-RNAs (miRNAs) have been proposed as potential accessible biomarkers for neurodegenerative diseases such as Parkinson's disease (PD). Here we analyzed the serum levels of 377 miRNAs in a discovery set of 10 idiopathic Parkinson's disease (IPD) patients, 10 PD patients carriers of the LRRK2 G2019S mutation (LRRK2 PD), and 10 controls by using real-time quantitative PCR-based TaqMan MicroRNA arrays. We detected candidate differentially expressed miRNAs, which were further tested in a first validation set consisting of 20 IPD, 20 LRRK2 PD, and 20 control samples. We found four statistically significant miRNAs that were downregulated in either LRRK2 or IPD (miR-29a, miR-29c, miR-19a, and miR-19b). Subsequently, we validated these findings in a third set of samples consisting of 65 IPD and 65 controls and confirmed the association of downregulated levels of miR-29c, miR-29a, and miR-19b in IPD. Differentially expressed miRNAs are predicted to target genes belonging to pathways related to ECM–receptor interaction, focal adhesion, MAPK, Wnt, mTOR, adipocytokine, and neuron projection. Results from our exploratory study indicate that downregulated levels of specific circulating serum miRNAs are associated with PD and suggest their potential use as noninvasive biomarkers for PD. Future studies should further confirm the association of these miRNAs with PD. © 2014 Wiley Periodicals, Inc.

Ancillary