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MicroRNA Analysis in the Spinal Fluid of Alzheimer Patients: A Methodological Feasibility Study

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Circulating Nucleic Acids in Plasma and Serum

Abstract

MicroRNAs form a novel class of functional biomolecules with a great potential to be used as informative biomarkers for clinical diagnostics such as for Alzheimer’s disease (AD). For this purpose, we tested the prerequisite: can microRNAs be isolated and quantified from the spinal fluid of patients at risk for or diagnosed with Alzheimer disease? Our data show that quantitative analysis of all currently known microRNA’s (n = 667) is technically possible in spinal fluid of patients with Alzheimer disease. For this, we applied the Megaplex protocol with Taqman Array MicroRNA cards on small RNA isolated with the MirVana Paris kit.

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Abbreviations

AD:

Alzheimer’s disease

CSF:

Cerebrospinal fluid

qRT-PCR:

Quantitative reverse transcriptase PCR

References

  • Barbato C, Giorgi C, Catalanotto C et al (2008) Thinking about RNA? MicroRNAs in the brain. Mamm Genome 19:541–551

    Article  PubMed  CAS  Google Scholar 

  • Bettens K, Brouwers N, Engelborghs S et al (2009) APP and BACE1 microRNA genetic variability has no major role in risk for Alzheimer disease. Hum Mutat 30:1207–1213

    Article  PubMed  CAS  Google Scholar 

  • Blennow K, Hampel H (2003) CSF markers for incipient Alzheimer’s disease. Lancet Neurol 2:605–613

    Article  PubMed  CAS  Google Scholar 

  • Boissonneault V, Plante I, Rivest S et al (2009) MicroRNA-298 and microRNA-328 regulate expression of mouse beta-amyloid precursor protein-converting enzyme 1. J Biol Chem 284:1971–1981

    Article  PubMed  CAS  Google Scholar 

  • Bouwman FH, Schoonenboom SNM, van der Flier WM et al (2007) CSF biomarkers and medial temporal lobe atrophy predict dementia in mild cognitive impairment. Neurobiol Aging 28:1070–1074

    Article  PubMed  CAS  Google Scholar 

  • Cataldo AM, Peterhoff CM, Troncoso JC et al (2000) Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer’s disease and down syndrome: differential effects of APOE genotype and presenilin mutations. Am J Pathol 157:277–286

    Article  PubMed  CAS  Google Scholar 

  • Chen C, Ridzon DA, Broomer AJ et al (2005) Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 33:e179–e188

    Article  PubMed  Google Scholar 

  • Christensen M, Schratt GM (2009) MicroRNA involvement in developmental and functional aspects of the nervous system and in neurological diseases. Neurosci Lett 466:55–62

    Article  PubMed  CAS  Google Scholar 

  • Cogswell JP, Ward J, Taylor IA et al (2008) Identification of microRNA changes in Alzheimer’s disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimers Dis 14:27–41

    PubMed  CAS  Google Scholar 

  • Faghihi MA, Modarresi F, Khalil AM et al (2008) Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of beta-secretase. Nat Med 14:723–730

    Article  PubMed  CAS  Google Scholar 

  • Graeber MB, Mehraein P (1999) Reanalysis of the first case of Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 249(Suppl 3):10–13

    Article  PubMed  Google Scholar 

  • Griffiths-Jones S, Saini HK, van Dongen S et al (2008) miRBase: tools for microRNA genomics. Nucleic Acids Res 36:D154–D158

    Article  PubMed  CAS  Google Scholar 

  • Hansson O, Zetterberg H, Buchhave P et al (2006) Association between CSF biomarkers and incipient Alzheimer’s disease in patients with mild cognitive impairment: a follow-up study. Lancet Neurol 5:228–234

    Article  PubMed  CAS  Google Scholar 

  • Hebert SS, Horre K, Nicolai L et al (2008) Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/beta-secretase expression. Proc Natl Acad Sci U S A 105:6415–6420

    Article  PubMed  CAS  Google Scholar 

  • Hebert SS, Horre K, Nicolai L et al (2009) MicroRNA regulation of Alzheimer’s Amyloid precursor protein expression. Neurobiol Dis 33:422–428

    Article  PubMed  CAS  Google Scholar 

  • Kimura R, Kamino K, Yamamoto M et al (2007) The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease. Hum Mol Genet 16:15–23

    Article  PubMed  CAS  Google Scholar 

  • Landgraf P, Rusu M, Sheridan R et al (2007) A mammalian microRNA expression atlas based on small RNA library sequencing. Cell 129:1401–1414

    Article  PubMed  CAS  Google Scholar 

  • Lau PW, MacRae IJ (2009) The molecular machines that mediate microRNA maturation. J Cell Mol Med 13:54–60

    Article  PubMed  CAS  Google Scholar 

  • Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854

    Article  PubMed  CAS  Google Scholar 

  • Lukiw WJ (2007) Micro-RNA speciation in fetal, adult and Alzheimer’s disease hippocampus. Neuroreport 18:297–300

    Article  PubMed  CAS  Google Scholar 

  • Lukiw WJ, Zhao Y, Cui JG (2008) An NF-kappaB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer disease and in stressed human brain cells. J Biol Chem 283:31315–31322

    Article  PubMed  CAS  Google Scholar 

  • Mattsson N, Zetterberg H, Hansson O et al (2009) CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 302:385–393

    Article  PubMed  CAS  Google Scholar 

  • McKhann G, Drachman D, Folstein M et al (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944

    Google Scholar 

  • Mitchell PS, Parkin RK, Kroh EM et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105:10513–101518

    Article  PubMed  CAS  Google Scholar 

  • Mraz M, Malinova K, Mayer J et al (2009) MicroRNA isolation and stability in stored RNA samples. Biochem Biophys Res Commun 390:1–4

    Article  PubMed  CAS  Google Scholar 

  • Mulder C, Verwey N, van der Flier W et al (2010) Amyloid-{beta}(1-42), Total Tau, and Phosphorylated Tau as cerebrospinal fluid biomarkers for the diagnosis of Alzheimer Disease. Clin Chem 56:248–253

    Article  PubMed  CAS  Google Scholar 

  • Naqvi AR, Islam MN, Choudhury NR et al (2009) The fascinating world of RNA interference. Int J Biol Sci 5:97–117

    Article  PubMed  CAS  Google Scholar 

  • Nelson PT, Braak H, Markesbery WR (2009) Neuropathology and cognitive impairment in Alzheimer disease: a complex but coherent relationship. J Neuropathol Exp Neurol 68:1–14

    Article  PubMed  CAS  Google Scholar 

  • Niwa R, Zhou F, Li C et al (2008) The expression of the Alzheimer’s amyloid precursor protein-like gene is regulated by developmental timing microRNAs and their targets in Caenorhabditis elegans. Dev Biol 315:418–425

    Article  PubMed  CAS  Google Scholar 

  • Nunez-Iglesias J, Liu CC, Morgan TE et al (2010) Joint genome-wide profiling of microRNA and mRNA expression in Alzheimer’s disease cortex reveals altered microRNA regulation. PLoS One 5:e8898. doi:10.1371/journal.pone.0008898

    Article  PubMed  Google Scholar 

  • Patel N, Hoang D, Miller N et al (2008) MicroRNAs can regulate human APP levels. Mol Neurodegener 3:10–16

    Article  PubMed  Google Scholar 

  • Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136:629–641

    Article  PubMed  CAS  Google Scholar 

  • Rana TM (2007) Illuminating the silence: understanding the structure and function of small RNAs. Nat Rev Mol Cell Biol 8:23–36

    Article  PubMed  CAS  Google Scholar 

  • Schoonenboom NSM, Pijnenburg YAL, Mulder C et al (2004) Amyloid beta(1-42) and phosphorylated tau in CSF as markers for early-onset alzheimer disease. Neurology 62:1580–1584

    Article  PubMed  CAS  Google Scholar 

  • Sethi P, Lukiw WJ (2009) Micro-RNA abundance and stability in human brain: specific alterations in Alzheimer’s disease temporal lobe neocortex. Neurosci Lett 459:100–104

    Article  PubMed  CAS  Google Scholar 

  • Verwey NA, van der Flier WM, Blennow K et al (2009) A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer’s disease. Ann Clin Biochem 46:235–240

    Article  PubMed  CAS  Google Scholar 

  • Visser PJ, Verhey F, Knol DL et al (2009) Prevalence and prognostic value of CSF markers of Alzheimer’s disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study. Lancet Neurol 8:619–627

    Article  PubMed  Google Scholar 

  • 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 28:1213–1223

    Article  PubMed  Google Scholar 

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Correspondence to Cees Oudejans .

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van Harten, A. et al. (2010). MicroRNA Analysis in the Spinal Fluid of Alzheimer Patients: A Methodological Feasibility Study. In: Gahan, P. (eds) Circulating Nucleic Acids in Plasma and Serum. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9382-0_37

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