Skip to main content
SpringerLink
Log in

microRNAs in Sporadic Alzheimer’s Disease and Related Dementias

  • Chapter
  • First Online:
Macro Roles for MicroRNAs in the Life and Death of Neurons

Part of the book series: Research and Perspectives in Neurosciences ((NEUROSCIENCE))

  • 434 Accesses

Abstract

Recent studies have demonstrated that non-coding microRNAs (miRNAs), which function at the posttranscriptional level as a rheostat of the transcriptome and proteome, control a variety of neuronal functions as well as neuronal survival.  Studies performed in humans support the idea that changes in miRNA expression profiles or target sequences could significantly contribute to the risk of major neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). MiRNAs seem to participate directly in the regulation of expression of AD-related genes, including APP and BACE1/β-secretase, which are involved in the neurotoxic Aβ peptide production; the latter accumulates in the brains of AD patients. This observation is interesting, as gene dosage effects of the APP gene can cause genetic AD. In this regard, miRNA research appears to be particularly promising for the understanding of the very frequent and poorly understood sporadic forms of AD and probably other neurological disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdelmohsen K, Srikantan S, Kuwano Y, Gorospe M (2008) miR-519 reduces cell proliferation by lowering RNA-binding protein HuR levels. Proc Natl Acad Sci USA 105:20297–20302

    Article  CAS  PubMed  Google Scholar 

  • Abelson JF, Kwan KY, O'Roak BJ, Baek DY, Stillman AA, Morgan TM, Mathews CA, Pauls DL, Rasin MR, Gunel M, Davis NR, Ercan-Sencicek AG, Guez DH, Spertus JA, Leckman JF, Dure LSt, Kurlan R, Singer HS, Gilbert DL, Farhi A, Louvi A, Lifton RP, Sestan N, State MW (2005) Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310:317–320

    Article  CAS  PubMed  Google Scholar 

  • Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355

    Article  CAS  PubMed  Google Scholar 

  • Barad O, Meiri E, Avniel A, Aharonov R, Barzilai A, Bentwich I, Einav U, Gilad S, Hurban P, Karov Y, Lobenhofer EK, Sharon E, Shiboleth YM, Shtutman M, Bentwich Z, Einat P (2004) MicroRNA expression detected by oligonucleotide microarrays: system establishment and expression profiling in human tissues. Genome Res 14:2486–2494

    Article  CAS  PubMed  Google Scholar 

  • Bettens K, Brouwers N, Engelborghs S, van Miegroet H, De Deyn P, Theuns J, Sleegers K, Van Broeckhoven C (2009) APP and BACE1 miRNA genetic variability has no major role in risk for Alzheimer's disease. Human Mutat, 30:1207–1213

    Article  CAS  Google Scholar 

  • Bilen J, Liu N, Burnett BG, Pittman RN, Bonini NM (2006) MicroRNA pathways modulate polyglutamine-induced neurodegeneration. Mol Cell 24:157–163

    Article  CAS  PubMed  Google Scholar 

  • Calin GA, Croce CM (2006) MicroRNA-cancer connection: the beginning of a new tale. Cancer Res 66:7390–7394

    Article  CAS  PubMed  Google Scholar 

  • Carrettiero DC, Hernandez I, Neveu P, Papagiannakopoulos T, Kosik KS (2009) The cochaperone BAG2 sweeps paired helical filament- insoluble tau from the microtubule. J Neurosci 29:2151–2161

    Article  CAS  PubMed  Google Scholar 

  • Cogswell JP, Ward J, Taylor IA, Waters M, Shi Y, Cannon B, Kelnar K, Kemppainen J, Brown D, Chen C, Prinjha RK, Richardson JC, Saunders AM, Roses AD, Richards CA (2008) Identification of miRNA changes in Alzheimer's disease brain and CSF yields putative biomarkers and insights into disease pathways. J Alzheimers Dis 14:27–41

    CAS  PubMed  Google Scholar 

  • Davis TH, Cuellar TL, Koch SM, Barker AJ, Harfe BD, McManus MT, Ullian EM (2008) Conditional loss of Dicer disrupts cellular and tissue morphogenesis in the cortex and hippocampus. J Neurosci 28:4322–4330

    Article  CAS  PubMed  Google Scholar 

  • Delacourte A, Buee L (2000. Tau pathology: a marker of neurodegenerative disorders. Curr Opin Neurol 13:371–376

    Article  CAS  PubMed  Google Scholar 

  • Eulalio A, Huntzinger E, Izaurralde E (2008) Getting to the root of miRNA-mediated gene silencing. Cell 132:9–14

    Article  CAS  PubMed  Google Scholar 

  • Fiore R, Khudayberdiev S, Christensen M, Siegel G, Flavell SW, Kim TK, Greenberg ME, Schratt G (2009) Mef2-mediated transcription of the miR379-410 cluster regulates activity-dependent dendritogenesis by fine-tuning Pumilio2 protein levels. EMBO J 28:697–710

    Article  CAS  PubMed  Google Scholar 

  • Fukumoto H, Cheung BS, Hyman BT, Irizarry MC (2002) ß-secretase protein and activity are increased in the neocortex in Alzheimer disease. Arch Neurol 59:1381–1389

    Article  PubMed  Google Scholar 

  • Haass C (2004) Take five--BACE and the r-secretase quartet conduct Alzheimer's amyloid ß-peptide generation. EMBO J 23:483–488

    Article  CAS  PubMed  Google Scholar 

  • Hébert SS, De Strooper B (2007) Molecular biology. miRNAs in neurodegeneration. Science 317:1179–1180

    Article  PubMed  Google Scholar 

  • Hébert SS, De Strooper B (2009) Alterations of the microRNA network cause neurodegenerative disease. Trends Neurosci 32:199–206

    Article  PubMed  Google Scholar 

  • Hébert SS, Horre K, Nicolai L, Papadopoulou AS, Mandemakers W, Silahtaroglu AN, Kauppinen S, Delacourte A, De Strooper B (2008) Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/ß-secretase expression. Proc Natl Acad Sci USA 105:6415–6420.

    Article  PubMed  Google Scholar 

  • Hébert SS, Horre K, Nicolai L, Bergmans B, Papadopoulou AS, Delacourte A, De Strooper B (2009) MicroRNA regulation of Alzheimer's amyloid precursor protein expression. Neurobiol Dis 33:422–428

    Article  PubMed  Google Scholar 

  • Kim J, Inoue K, Ishii J, Vanti WB, Voronov SV, Murchison E, Hannon G, Abeliovich A (2007) A MicroRNA feedback circuit in midbrain dopamine neurons. Science 317:1220–1224

    Article  CAS  PubMed  Google Scholar 

  • Kuhn DE, Nuovo GJ, Martin MM, Malana GE, Pleister AP, Jiang J, Schmittgen TD, Terry AV, Jr., Gardiner K, Head E, Feldman DS, Elton TS (2008) Human chromosome 21-derived miRNAs are overexpressed in down syndrome brains and hearts. Biochem Biophys Res Commun 370:473–477

    Article  CAS  PubMed  Google Scholar 

  • Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN (2004) MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23:4051–4060

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Miska EA, Alvarez-Saavedra E, Townsend M, Yoshii A, Sestan N, Rakic P, Constantine-Paton M, Horvitz HR (2004) Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol 5:R68

    Article  PubMed  Google Scholar 

  • Patel N, Hoang D, Miller N, Ansaloni S, Huang Q, Rogers JT, Lee JC, Saunders AJ (2008) MicroRNAs can regulate human APP levels. Mol Neurodegener 3:10

    Article  PubMed  Google Scholar 

  • Perkins DO, Jeffries CD, Jarskog LF, Thomson JM, Woods K, Newman MA, Parker JS, Jin J, Hammond SM (2007) microRNA expression in the prefrontal cortex of individuals with schizophrenia and schizoaffective disorder. Genome Biol 8:R27

    Article  PubMed  Google Scholar 

  • Rademakers R, Eriksen JL, Baker M, Robinson T, Ahmed Z, Lincoln SJ, Finch N, Rutherford NJ, Crook RJ, Josephs KA, Boeve BF, Knopman DS, Petersen RC, Parisi JE, Caselli RJ, Wszolek ZK, Uitti RJ, Feldman H, Hutton ML, Mackenzie IR, Graff-Radford NR, Dickson DW (2008) Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Human Mol Genet 17:3631–3642

    Article  CAS  Google Scholar 

  • Schaefer A, O'Carroll D, Tan CL, Hillman D, Sugimori M, Llinas R, Greengard P (2007) Cerebellar neurodegeneration in the absence of microRNAs. J Exp Med 204:1553–1558

    Article  CAS  PubMed  Google Scholar 

  • Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, Greenberg ME (2006) A brain-specific microRNA regulates dendritic spine development. Nature 439:283–289

    Article  CAS  PubMed  Google Scholar 

  • Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5:R13

    Article  PubMed  Google Scholar 

  • Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K (2003) a-Synuclein locus triplication causes Parkinson's disease. Science 302:841

    Article  CAS  PubMed  Google Scholar 

  • Vassar R (2001) The ß-secretase, BACE: a prime drug target for Alzheimer's disease. J Mol Neurosci 17:157–170

    Article  CAS  PubMed  Google Scholar 

  • Wang G, van der Walt JM, Mayhew G, Li YJ, Zuchner S, Scott WK, Martin ER, Vance JM (2008) Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of a-synuclein. Am J Human Genet 82:283–289

    Article  CAS  Google Scholar 

  • Wang WX, Rajeev BW, Stromberg AJ, Ren N, Tang G, Huang Q, Rigoutsos I, Nelson PT (2008) The expression of microRNA miR-107 decreases early in Alzheimer's disease and may accelerate disease progression through regulation of ß-site amyloid precursor protein-cleaving enzyme 1. J Neurosci 28:1213–1223

    Article  PubMed  Google Scholar 

  • Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY, Yang JR, Su H, Zhuang SM (2008) A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis 29:2126–2131

    Article  CAS  PubMed  Google Scholar 

  • Yang LB, Lindholm K, Yan R, Citron M, Xia W, Yang XL, Beach T, Sue L, Wong P, Price D, Li R, Shen Y (2003) Elevated ß-secretase expression and enzymatic activity detected in sporadic Alzheimer disease. Nature Med 9:3–4

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Département de Biologie médicale, Centre de Recherche du CHUQ (CHUL), Axe Neurosciences, Université Laval, 2705 Boul. Laurier, Québec G1V 4G2, Local RC-9800, Québec, Qc, Canada

    Sébastien S. Hébert

Authors
  1. Sébastien S. Hébert
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wim Mandemakers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aikaterini S. Papadopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bart DeStrooper
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sébastien S. Hébert .

Editor information

Editors and Affiliations

  1. Center Human Genetics, Katholieke Universiteit Leuven, Herestraat 49, Leuven, 3000, Belgium

    Bart De Strooper

  2. Recherche Therapeutique, Fondation IPSEN pour la, quai George Gorse 65, Boulogne Billancourt Cedex, 92650, France

    Yves Christen

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Hébert, S.S., Mandemakers, W., Papadopoulou, A.S., DeStrooper, B. (2010). microRNAs in Sporadic Alzheimer’s Disease and Related Dementias. In: De Strooper, B., Christen, Y. (eds) Macro Roles for MicroRNAs in the Life and Death of Neurons. Research and Perspectives in Neurosciences. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-04298-0_10

Download citation

Publish with us

Policies and ethics

Search

Navigation