Skip to main content

Advertisement

SpringerLink
Log in

Secretases-related miRNAs in Alzheimer’s disease: new approach for biomarker discovery

  • Review Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Amyloid-β (Aβ) as a crucial factor in pathogenesis of Alzheimer’s disease (AD) is derived from amyloid precursor protein (APP) through a proteolytic process catalyzing by β- and γ-secretase—in amyloidogenesis pathway. Products of α-secretase cleavage also have protective effects against Aβ toxicity. According to existing evidences, microRNAs (miRNAs) show a unique pattern of expression in AD. Moreover, miRNAs regulatory effects on expression of secretases and their main components have been demonstrated in AD. The miRNAs levels may be changed in preclinical conditions and may be considered as diagnostic biomarkers in AD. Therefore, in this paper, we review the miRNAs involved in APP cleavage pathways and the formation of Aβ in order to evaluate the potential diagnostic biomarkers in AD.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Schonrock N, Matamales M, Ittner LM, Gotz J (2012) MicroRNA networks surrounding APP and amyloid-β metabolism—implications for Alzheimer’s disease. Exp Neurol 235:447–454

    Article  CAS  PubMed  Google Scholar 

  2. Povova J, Ambroz P, Bar M, Pavulova V, Sery O, Tomaskova H, Janout V (2012) Epidemiological of and risk factor for Alzheimer’s disease: a review. Biomed Pep Med Fac Univ Palacky Olomouc Czech Repub 156(2):108–114

    Article  Google Scholar 

  3. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 8(2):101–112

    Article  CAS  PubMed  Google Scholar 

  4. Kuhn P, Wang H, Dislich B, Colombo A, Zeitschel U, Ellwart JW, Kremmer E, RoBner S, Lichtenthaler SF (2010) ADAM10 is the physiologically relevant, constitutive alpha-secretase of the amyloid precursor protein in primary neurons. EMBO J 29(17):3020–3032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Femminella GD, Ferrara N, Rengo G (2015) The emerging role of microRNAs in Alzheimer’s disease. Front Physiol 6(40)

  6. Berti V, Polito C, Lombardi G, Ferrari C, Sorbi S, Pupi A (2016) Rethinking on the concept of biomarkers in preclinical Alzheimer’s disease. Neurol Sci 37:663–672

    Article  PubMed  Google Scholar 

  7. Geekiyanage H, Jicha GA, Nelson PT, Chan C (2012) Blood serum miRNA: non-invasive biomarkers for Alzheimer’s disease. Neurol Sci 235(2):491–496

    CAS  Google Scholar 

  8. During EH, Osorio RS, Elahi FM, Mosconi L, de Leon MJ (2011) The concept of FDG-PET endophenotype in Alzheimer’s disease. Neurol Sci 32:559–569

    Article  PubMed  Google Scholar 

  9. Toledo JB, Show LM, Trojanowski JQ (2013) Plasma amyloid beta measurements - a desired but elusive Alzheimer’s disease biomarker. Alzheimers res Ther 5(2):8

  10. Jin XF, Wu N, Wang L, Li J (2013) Circulating microRNAs: a novel class of potential biomarkers for diagnosing and prognosing central nervous system diseases. Cell Mol Neurobiol 33(5):601–613

    Article  CAS  PubMed  Google Scholar 

  11. Hebert SS, Horré K, Nicolai L, Papadopoulou AS, Mandemakers W, Silahtaroglu NA, Kauppinen S, Delacourte A, Strooper BD (2008) Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer’s disease correlates with increased BACE1/ -secretase expression. Proc Natl Acad Sci U S A 105(17):6415–6420

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Rooij EV, Kauppinen S (2014) Development of microRNA therapeutics is coming of age. EMBO Mol Med 8(12):1361–1471

    Google Scholar 

  13. Haass C (2004) Take five-BACE and the gamma-secretase quartet conduct Alzheimer’s amyloid beta-peptide generation. EMBO J 23(3):483–488

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. He G, Luo W, Li P, Remmers C, Netzer WJ, Hendrick J, Bettayeb K, Flajolet M, Gorelick F, Greengard W, Greengard P (2010) Gamma-secretase activating protein is a therapeutictarget for Alzheimer’s disease. Nature 467:95–98

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Krichevsky AM, King KS, Donahue CP, Khrapko K, Kosik KS (2003) A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9:1274–1281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ikeda K, Urakami K, Arai H, Wada K, Ji Y, Adachi Y, Okada A, Kowa H, Sasaki H, Ohno K, Ohtsuka Y, Ishikawa Y, Nakashima K (2000) The expression of Presenilin 1 mRNA in skin fibroblasts and brains from sporadic Alzheimer’s disease. Dement Geriatr Cogn Disord 11:245–250

    Article  CAS  PubMed  Google Scholar 

  17. Jayadev S, Case A, Alajajian B, Moller ET, Garden GA (2013) Presenilin 2 influences miR146 level and activity in microglia. J Neurochem 127(5):592–599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Galimberti D, Villa C, Fenoglio C, Serpente M, Ghezzi L, Cioffi S, Arighi A, Fumagalli G, Scarpini E (2014) Circulating miRNAs as potential biomarkers in Alzheimer’s disease. J Alzheimers Dis 42(4):1261–1267

    CAS  PubMed  Google Scholar 

  19. Sorbi S, Nacmias B, Forleo P, Latorraca S, Gobbini I, Bracco L, Piacentini S, Amaducci L (1994) ApoE allele frequencies in Italian sporadic and familial Alzheimer’s disease. Neurosci Lett 177(1–2):100–102

    Article  CAS  PubMed  Google Scholar 

  20. Orlacchio A, Kawarai T, Polidoro M, Stefani A, Orlacchio A, George-Hyslpo PH, Bernardi G (2002) Association analysis between Alzheimer’s disease and the Nicastrin gene polymorphisms. Neurosci Lett 333(2):115–118

    Article  CAS  PubMed  Google Scholar 

  21. Delay C, Dorval V, Fok A, Grenier-Boley LJC, Hsiung GY, Hebert SS (2014) MicroRNAs targeting Nicastrin regulate Aβ production and areaffected by target site polymorphisms. Front Mol Neurosci 7:67

    Article  PubMed  PubMed Central  Google Scholar 

  22. Paris S, Smith PY, Goupil C, Dorval V, Hebert SS (2015) Preclinical evaluation of miR-15/107 family members as multifactorial drug targets for Alzheimer’s disease. Mol Ther Nucleic Acids 4(10):e256

    Article  Google Scholar 

  23. Liu W, Liu C, Zhu J, Shu P, Yin B, Gong Y, Qiang B, Yuan J, Peng X (2012) MicroRNA-16 targets amyloid precursor protein to potentially modulate Alzheimer’s-associated pathogenesis in SAMP8 mice. Neurobiol Aging 33(3):522–534

    Article  CAS  PubMed  Google Scholar 

  24. Mallick B, Ghosh Z (2011) A complex crosstalk between polymorphic microRNA target sites and AD prognosis. RNA Biol 8(4):665–673

    Article  CAS  PubMed  Google Scholar 

  25. Fatica A, Bozzoni I (2014) Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Neurol 15(1):7–21

    Article  CAS  Google Scholar 

  26. Kim J, Yoon H, Chung D, Brown JL, Belmonte K, Kim J (2016) miR-186 is decreased in aged brain and suppresses BACE1 expression. J Neurochem 137(3):436–445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yang G, Song Y, Zhou X, Deng Y, Liu T, Weng G, Yu D, Pan S (2015) MicroRNA-29c targets β-site amyloid precursor protein-cleaving enzyme 1 and has a neuroprotective role in vitro and in vivo. Mol Med Rep 12(2):3081–3088

    Article  CAS  PubMed  Google Scholar 

  28. Lei X, Lei L, Zhang Z, Zhang Z, Cheng Y (2015) Downregulated miR-29c correlates with increased BACE1 expression in sporadic Alzheimer’s disease. Int J Clin Exp Pathol 8(2):1565–1574

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Muller M, Jakel L, Bruinsma IB, Claassen JA, Kuiperij HB, Verbeek MM (2016) MicroRNA-29a is a candidate biomarker for Alzheimer’s disease in cell-free cerebrospinal fluid. Mol Neurobiol 53(5):2894–2899

    Article  PubMed  Google Scholar 

  30. Tan L, Yu JT, Liu QY, Tan MS, Zhang W, Hu N, Wang YL, Sun L, Jiang T, Tan L (2014) Circulating miR-125b as a biomarker of Alzheimer’s disease. J Neurol Sci 336(1–2):52–56

    Article  CAS  PubMed  Google Scholar 

  31. Dangla-Valls A, Molinuevo JL, Altirriba J, Sanchez-Valle R, Alcolea D, Fortea J, Rami L, Balasa M, Munoz-Garcia C, Ezquerra M, Fernandez-Santiago R, Lleo A, Antonell A (2016) CSF microRNA profiling in Alzheimer’s disease: a screening and validation study. Mol Neurobiol:1–8

  32. Chen Y, Huang X, Zhang YW, Rockenstein E, Bu G, Golde TE, Masliah E, Xu H (2012) Alzheimer’s β-secretase (BACE1) regulates the cAMP/PKA/CREB pathway independently of β-amyloid. J Neurosci 32(33):11390–11395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhu HC, Wang LM, Wang M, Song B, Tan S, Teng JF, Duan DX (2012) MicroRNA-195 downregulates Alzheimer’s disease amyloid-β production by targeting BACE1. Brain Res Bull 88(6):596–601

    Article  CAS  PubMed  Google Scholar 

  34. Ai J, Sun LH, Che H, Zhang R, Zhang TZ, Wu WC, Su XL, Chen X, Yang G, Li K, Wang N, Ban T, Bao YN, Guo F, Niu HF, Zhu YL, Zhu XY, Zhao SG, Yang BF (2013) MicroRNA-195 protects against dementia induced by chronic brain hypoperfusion via its anti-amyloidogenic effect in rats. J Neurosci 33(9):3989–4001

    Article  CAS  PubMed  Google Scholar 

  35. Geekiyanage H, Jicha GA, Nelson PT, Chan C (2012) Blood serum miRNA: non-invasive biomarkers for Alzheimer’s disease. Exp Neurol 235(2):491–496

    Article  CAS  PubMed  Google Scholar 

  36. Sørensen SS, Nygaard AB, Christensen T (2016) miRNA expression profiles in cerebrospinal fluid and blood of patients with Alzheimer’s disease and other types of dementia - an exploratory study. Transl Neurodegener 5:6

  37. Fang M, Wang J, Zhang X, Geng Y, Hu Z, Rudd JA, Ling S, Chen W, Hun S (2012) The miR-124 regulates the expression of BACE1/ -secretase correlated with cell death in Alzheimer’s disease. Toxicol Lett 209(1):94–105

    Article  CAS  PubMed  Google Scholar 

  38. Smith P, Hashimi AA, Girard J, Delay C, Hebert SS (2010) In vivo regulation of amyloid precursor protein neuronal splicing by microRNAs. J Neurochem 116(2):240–247

    Article  PubMed  Google Scholar 

  39. Liu CG, Wang JL, Li L, Wang PC (2014) MicroRNA-384 regulates both amyloid precursor protein and β-secretase expression and is a potential biomarker for Alzheimer’s disease. Int J Mol Med 34(1):160–166

    Article  PubMed  Google Scholar 

  40. Endres K, Fahrenholz F (2012) Regulation of alpha-secretase ADAM10 expression and activity. Exp Brain Res 217(3):343–352

    Article  CAS  PubMed  Google Scholar 

  41. Augustin R, Endres K, Reinhardt S, Kuhn P, Lichtenthaler SF, Hansen J, Wurst W, Trumbach D (2012) Computational identification and experimental validation of microRNAs binding to the Alzheimer-related gene ADAM10. BMC Med Genet 13(1):35–46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

    Seyedeh Nazanin Hajjari

  2. Cellular and Molecular Research Center, Department of Anatomy, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

    Mehdi Mehdizadeh

  3. Neurosisciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Saeed Sadigh-Eteghad

  4. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Dariush Shanehbandi & Behzad Baradaran

  5. Department of Medical Genetics, Iran University of Medical Sciences, Tehran, Iran

    Shahram Teimourian

Authors
  1. Seyedeh Nazanin Hajjari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mehdi Mehdizadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Saeed Sadigh-Eteghad
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dariush Shanehbandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shahram Teimourian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Behzad Baradaran
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Behzad Baradaran.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hajjari, S.N., Mehdizadeh, M., Sadigh-Eteghad, S. et al. Secretases-related miRNAs in Alzheimer’s disease: new approach for biomarker discovery. Neurol Sci 38, 1921–1926 (2017). https://doi.org/10.1007/s10072-017-3086-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-017-3086-3

Keywords

Search

Navigation