Export file:


  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text


  • Citation Only
  • Citation and Abstract

Parkinsons Disease-related Circulating microRNA Biomarkers——a Validation Study

1 Molecular Diagnostics Program, College of Health Professions, Ferris State University, Grand Rapids, MI 49503, USA;
2 Department of Cell and Molecular Biology, Grand Valley State University, Grand Rapids, MI 49503, USA;
3 School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;
4 Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87 Umeå, Sweden

Special Issues: Biofluid Biomarkers for Parkinson’s Disease

Parkinson's disease (PD) is the second most common neurodegenerative disease. One of the major challenges in studying this progressive neurological disorder is to identify and develop biomarkers for early detection. Recently, several blood-based microRNA (miRNA) biomarkers for PD have been reported. However, follow-up studies with new, independent cohorts have been rare. Previously, we identified a panel of four circulating miRNA biomarkers for PD (miR-1826, miR-450b-3p, miR-505, and miR-626) with biomarker performance of 91% sensitivity and 100% specificity. However, the expression of miR-450b-3p could not be detected in a new, independent validation set. In our current study, we improved the detection power by including a non-biased pre-amplification step in quantitative real-time PCR (qRT-PCR) and reevaluated the biomarker performance. We found the panel of four PD-related miRNAs achieved the predictive power of 83% sensitivity and 75% specificity in our validation set. This is the first biomarker validation study of PD which showed reproducibility and robustness of plasma-based circulating miRNAs as molecular biomarkers and qRT-PCR as potential diagnostic assay.
  Article Metrics

Keywords Parkinson's disease; circulating microRNAs; plasma; biomarkers; validation; quantitative real-time PCR

Citation: David Petillo, Stephen Orey, Aik Choon Tan, Lars Forsgren, Sok Kean Khoo. Parkinsons Disease-related Circulating microRNA Biomarkers——a Validation Study. AIMS Medical Science, 2015, 2(1): 7-14. doi: 10.3934/medsci.2015.1.7


  • 1. Margis R, Rieder CR (2011) Identification of blood microRNAs associated to Parkinsonis disease. J biotechnol 152: 96-101.    
  • 2. Martins M, Rosa A, Guedes LC, et al. (2011) Convergence of miRNA expression profiling, alpha-synuclein interacton and GWAS in Parkinson's disease. PloS one 6: e25443.    
  • 3. Khoo SK, Petillo D, Kang UJ, et al. (2012) Plasma-based circulating microRNA biomarkers for Parkinson's disease. J Parkinson Dis 2: 321-331.
  • 4. Cardo LF, Coto E, de Mena L, et al. (2013) Profile of microRNAs in the plasma of Parkinson's disease patients and healthy controls. J Neurol 260: 1420-1422.    
  • 5. Soreq L, Salomonis N, Bronstein M, et al. (2013) Small RNA sequencing-microarray analyses in Parkinson leukocytes reveal deep brain stimulation-induced splicing changes that classify brain region transcriptomes. Front Mol Neurosci 6: 10.
  • 6. Vallelunga A, Ragusa M, Di Mauro S, et al. (2014) Identification of circulating microRNAs for the differential diagnosis of Parkinson's disease and Multiple System Atrophy. Front Cell Neurosci8: 156.
  • 7. Botta-Orfila T, Morato X, Compta Y, et al. (2014) Identification of blood serum micro-RNAs associated with idiopathic and LRRK2 Parkinson's disease. J Neurosci Res 92: 1071-1077.    
  • 8. Burgos K, Malenica I, Metpally R, et al. (2014) Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology. PLoS One 9: e94839.    
  • 9. Khoo SK, Neuman LA, Forsgren L, et al. (2013) Could miRNA expression changes be a reliable clinical biomarker for Parkinson's disease? Neurodegener Dis Manag 3: 455-465.    
  • 10. Kroh EM, Parkin RK, Mitchell PS, et al. (2010) Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods 50: 298-301.    
  • 11. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25: 402-408.    
  • 12. Warnock DG, Peck CC (2010) A roadmap for biomarker qualification. Nat Biotechnol 28:444-445.    
  • 13. Tan AC, Naiman DQ, Xu L, et al. (2005) Simple decision rules for classifying human cancers from gene expression profiles. Bioinformatics 21: 3896-3904.    
  • 14. Paulovich AG, Whiteaker JR, Hoofnagle AN, et al. (2008) The interface between biomarker discovery and clinical validation: The tar pit of the protein biomarker pipeline. Proteomics Clin Appl 2: 1386-1402.    


This article has been cited by

  • 1. Sok Kean Khoo, Biofluid-based Biomarkers for Parkinson's Disease: A New Paradigm, AIMS Medical Science, 2015, 2, 4, 371, 10.3934/medsci.2015.4.371
  • 2. Meire Silva Batistela, Nalini Drieli Josviak, Carla Daniela Sulzbach, Ricardo Lehtonen Rodrigues de Souza, An overview of circulating cell-free microRNAs as putative biomarkers in Alzheimer's and Parkinson's Diseases, International Journal of Neuroscience, 2016, 1, 10.1080/00207454.2016.1209754
  • 3. Zahra Aghili, Navid Nasirizadeh, Adeleh Divsalar, Shahram Shoeibi, Parichehreh Yaghmaei, A highly sensitive miR-195 nanobiosensor for early detection of Parkinson’s disease, Artificial Cells, Nanomedicine, and Biotechnology, 2017, 1, 10.1080/21691401.2017.1411930
  • 4. Zhi Wen, Jie Zhang, Peng Tang, Ning Tu, Ke Wang, Guangyao Wu, Overexpression of miR‑185 inhibits autophagy and apoptosis of dopaminergic neurons by regulating the AMPK/mTOR signaling pathway in Parkinson's disease, Molecular Medicine Reports, 2017, 10.3892/mmr.2017.7897

Reader Comments

your name: *   your email: *  

Copyright Info: 2015, Sok Kean Khoo, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

Download full text in PDF

Export Citation

Copyright © AIMS Press All Rights Reserved