Circulating MicroRNAs in the Cerebrospinal Fluid of Patients with Brain Diseases

  • Akira Machida
  • Takuya Ohkubo
  • Takanori Yokota
Part of the Methods in Molecular Biology book series (MIMB, volume 1024)


MicroRNAs (miRNAs) are small, noncoding regulatory RNAs that regulate gene expression at the ­posttranscriptional level. Although circulating miRNAs in human body fluids have recently been recognized as disease biomarkers, especially in the field of oncology, little is known about the miRNAs in cerebrospinal fluid (CSF). This chapter describes the feasibility of miRNAs in CSF as biomarkers for the diagnosis of brain diseases and the methods of miRNA isolation from CSF.

Key words

microRNA Cerebrospinal fluid Neurodegenerative disease Biomarkers Internal control miRNA in CSF 


  1. 1.
    Campbell WW (2005) DeJong’s the neurological examination, 6th edn. Lippincott Williams & WilkinsGoogle Scholar
  2. 2.
    Ha TY (2011) MicroRNAs in human diseases: from autoimmune diseases to skin, psychiatric and neurodegenerative diseases. Immune Netw 11:227–244PubMedCrossRefGoogle Scholar
  3. 3.
    Ha TY (2011) The role of microRNAs in regulatory T cells and in the immune response. Immune Netw 11:11–41PubMedCrossRefGoogle Scholar
  4. 4.
    Tomankova T, Petrek M, Kriegova E (2010) Involvement of microRNAs in physiological and pathological processes in the lung. Respir Res 11:159PubMedCrossRefGoogle Scholar
  5. 5.
    Pallante P, Visone R, Croce CM et al (2010) Deregulation of microRNA expression in follicular-cell-derived human thyroid carcinomas. Endocr Relat Cancer 17:F91–F104PubMedCrossRefGoogle Scholar
  6. 6.
    Siegel SR, Mackenzie J, Chaplin G et al (2012) Circulating microRNAs involved in multiple sclerosis. Mol Biol Rep 39:6219–6225PubMedCrossRefGoogle Scholar
  7. 7.
    Thamilarasan M, Koczan D, Hecker M et al (2012) MicroRNAs in multiple sclerosis and experimental autoimmune encephalomyelitis. Autoimmun Rev 11:174–179PubMedCrossRefGoogle Scholar
  8. 8.
    Keller A, Leidinger P, Lange J et al (2009) Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls. PLoS One 4:e7440PubMedCrossRefGoogle Scholar
  9. 9.
    Maes OC, Chertkow HM, Wang E et al (2009) MicroRNA: implications for Alzheimer disease and other human CNS disorders. Curr Genomics 10:154–168PubMedCrossRefGoogle Scholar
  10. 10.
    Wang WX, Rajeev BW, Stromberg AJ et al (2008) The expression of microRNA miR-107 decreases early in Alzheimer’s disease and may accelerate disease progression through regulation of beta-site amyloid precursor protein-cleaving enzyme 1. J Neurosci 28:1213–1223PubMedCrossRefGoogle Scholar
  11. 11.
    Provost P (2010) MicroRNAs as a molecular basis for mental retardation, Alzheimer’s and prion diseases. Brain Res 1338:58–66PubMedCrossRefGoogle Scholar
  12. 12.
    Kim J, Inoue K, Ishii J et al (2007) A MicroRNA feedback circuit in midbrain dopamine neurons. Science 317:1220–1224PubMedCrossRefGoogle Scholar
  13. 13.
    Mouradian MM (2012) MicroRNAs in Parkinson’s disease. Neurobiol Dis 46:279–284PubMedCrossRefGoogle Scholar
  14. 14.
    Packer AN, Xing Y, Harper SQ et al (2008) The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is ­downregulated in Huntington’s disease. J Neurosci 28:14341–14346PubMedCrossRefGoogle Scholar
  15. 15.
    Williams AH, Valdez G, Moresi V et al (2009) MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. Science 326:1549–1554PubMedCrossRefGoogle Scholar
  16. 16.
    Abelson JF, Kwan KY, O’Roak BJ et al (2005) Sequence variants in SLITRK1 are associated with Tourette’s syndrome. Science 310:317–320PubMedCrossRefGoogle Scholar
  17. 17.
    Kuhn DE, Nuovo GJ, Martin MM et al (2008) Human chromosome 21-derived miRNAs are overexpressed in Down syndrome brains and hearts. Biochem Biophys Res Commun 370:473–477PubMedCrossRefGoogle Scholar
  18. 18.
    Mouillet-Richard S, Baudry A, Launay JM et al (2012) MicroRNAs and depression. Neurobiol Dis 46:272–278PubMedCrossRefGoogle Scholar
  19. 19.
    Perkins DO, Jeffries CD, Jarskog LF et al (2007) microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol 8:R27PubMedCrossRefGoogle Scholar
  20. 20.
    Beveridge NJ, Gardiner E, Carroll AP et al (2010) Schizophrenia is associated with an increase in cortical microRNA biogenesis. Mol Psychiatry 15:1176–1189PubMedCrossRefGoogle Scholar
  21. 21.
    Chen X, Liang H, Zhang J et al (2012) Horizontal transfer of microRNAs: molecular mechanisms and clinical applications. Protein Cell 3:28–37PubMedCrossRefGoogle Scholar
  22. 22.
    Baraniskin A, Kuhnhenn J, Schlegel U et al (2011) Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system. Blood 117:3140–3146PubMedCrossRefGoogle Scholar
  23. 23.
    Baraniskin A, Kuhnhenn J, Schlegel U et al (2012) Identification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma. Neuro Oncol 14:29–33PubMedCrossRefGoogle Scholar
  24. 24.
    Teplyuk NM, Mollenhauer B, Gabriely G et al (2012) MicroRNAs in cerebrospinal fluid identify glioblastoma and metastatic brain cancers and reflect disease activity. Neuro Oncol 14:689–700PubMedCrossRefGoogle Scholar
  25. 25.
    Cogswell JP, Ward J, Taylor IA et al (2008) Identification of miRNA changes in Alzheimer’s disease brain and CSF yields putative ­biomarkers and insights into disease pathways. J Alzheimers Dis 14:27–41PubMedGoogle Scholar
  26. 26.
    Gallego JA, Gordon ML, Claycomb K et al (2012) In vivo microRNA detection and quantitation in cerebrospinal fluid. J Mol Neurosci 47:243–248PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Akira Machida
    • 1
  • Takuya Ohkubo
    • 1
  • Takanori Yokota
    • 1
  1. 1.Department of Neurology and Neurological Science, Graduate School of MedicineTokyo Medical and Dental UniversityTokyoJapan

Personalised recommendations