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A Customized Quantitative PCR MicroRNA Panel Provides a Technically Robust Context for Studying Neurodegenerative Disease Biomarkers and Indicates a High Correlation Between Cerebrospinal Fluid and Choroid Plexus MicroRNA Expression

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Abstract

MicroRNA (miRNA) expression varies in association with different tissue types and in diseases. Having been found in body fluids including blood and cerebrospinal fluid (CSF), miRNAs constitute potential biomarkers. CSF miRNAs have been proposed as biomarkers for neurodegenerative diseases; however, there is a lack of consensus about the best candidate miRNA biomarkers and there has been variability in results from different research centers, perhaps due to technical factors. Here, we sought to optimize technical parameters for CSF miRNA studies. We examined different RNA isolation methods and performed miRNA expression profiling with TaqMan® miRNA Arrays. More specifically, we developed a customized CSF-miRNA low-density array (TLDA) panel that contains 47 targets: miRNAs shown previously to be relevant to neurodegenerative disease, miRNAs that are abundant in CSF, data normalizers, and controls for potential blood and tissue contamination. The advantages of using this CSF-miRNA TLDA panel include specificity, sensitivity, fast processing and data analysis, and cost effectiveness. We optimized technical parameters for this assay. Further, the TLDA panel can be tailored to other specific purposes. We tested whether the profile of miRNAs in the CSF resembled miRNAs isolated from brain tissue (hippocampus or cerebellum), blood, or the choroid plexus. We found that the CSF miRNA expression profile most closely resembles that of choroid plexus tissue, underscoring the potential importance of choroid plexus-derived signaling through CSF miRNAs. In summary, the TLDA miRNA array panel will enable evaluation and discovery of CSF miRNA biomarkers and can potentially be utilized in clinical diagnosis and disease stage monitoring.

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Acknowledgements

Sincere thanks to the research subjects, clinicians, and staff at the UK-ADC. Funding was provided through NIH grants P30 AG028383, R01 AG 042419, and R21 NS085830.

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Authors and Affiliations

  1. Sanders Brown Center on Aging, University of Kentucky, Lexington, KY, 40536, USA

    Wang-Xia Wang, David W. Fardo, Gregory A. Jicha & Peter T. Nelson

  2. Department of Biostatistics, University of Kentucky, Lexington, KY, 40536, USA

    David W. Fardo

  3. Department of Neurology, University of Kentucky, Lexington, KY, 40536, USA

    Gregory A. Jicha

  4. Department of Pathology, Division of Neuropathology, University of Kentucky, Lexington, KY, 40536, USA

    Peter T. Nelson

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  1. Wang-Xia Wang
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  2. David W. Fardo
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Correspondence to Wang-Xia Wang or Peter T. Nelson.

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Wang, WX., Fardo, D.W., Jicha, G.A. et al. A Customized Quantitative PCR MicroRNA Panel Provides a Technically Robust Context for Studying Neurodegenerative Disease Biomarkers and Indicates a High Correlation Between Cerebrospinal Fluid and Choroid Plexus MicroRNA Expression. Mol Neurobiol 54, 8191–8202 (2017). https://doi.org/10.1007/s12035-016-0316-2

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