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.

Document Type

Article

Publication Date

12-2017

Notes/Citation Information

Published in Molecular Neurobiology, v. 54, issue 10, p. 8191–8202.

© Springer Science+Business Media New York 2016

The copyright holder has granted the permission for posting the article here.

The document available for download is the authors' post-peer-review final draft of the article.

Digital Object Identifier (DOI)

https://doi.org/10.1007/s12035-016-0316-2

Funding Information

Funding was provided through NIH grants P30 AG028383, R01 AG 042419, and R21 NS085830.

Related Content

The online version of this article (doi: 10.1007/s12035-016-0316-2) contains supplementary material, which is available to authorized users.

NIHMS840284-supplement-supp_fig_1.pptx (59 kB)
Supplemental Material Figure 1

NIHMS840284-supplement-supp_fig_2.pptx (59 kB)
Supplemental Material Figure 2

NIHMS840284-supplement-supp_Tables.xlsx (110 kB)
Supplemental Material Files

NIHMS840284-supplement-Suppl_Tables_1-3.docx (62 kB)
Supplemental Material Tables 1-3

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