MicroRNA Profiling of CSF Reveals Potential Biomarkers to Detect Alzheimer`s Disease
Language: 
English
Abstract: 

The miRBase-21 database currently lists 1881 microRNA (miRNA) precursors and 2585 unique mature human miRNAs. Since their discovery, miRNAs have proved to present a new level of epigenetic post-transcriptional control of protein synthesis. Initial results point to a possible involvement of miRNA in Alzheimer's disease (AD). We applied OpenArray technology to profile the expression of 1178 unique miRNAs in cerebrospinal fluid (CSF) samples of AD patients (n = 22) and controls (n = 28). Using a Cq of 34 as cut-off, we identified positive signals for 441 miRNAs, while 729 miRNAs could not be detected, indicating that at least 37% of miRNAs are present in the brain. We found 74 miRNAs being down- and 74 miRNAs being up-regulated in AD using a 1.5 fold change threshold. By applying the new explorative "Measure of relevance" method, 6 reliable and 9 informative biomarkers were identified. Confirmatory MANCOVA revealed reliable miR-100, miR-146a and miR-1274a as differentially expressed in AD reaching Bonferroni corrected significance. MANCOVA also confirmed differential expression of informative miR-103, miR-375, miR-505#, miR-708, miR-4467, miR-219, miR-296, miR-766 and miR-3622b-3p. Discrimination analysis using a combination of miR-100, miR-103 and miR-375 was able to detect AD in CSF by positively classifying controls and AD cases with 96.4% and 95.5% accuracy, respectively. Referring to the Ingenuity database we could identify a set of AD associated genes that are targeted by these miRNAs. Highly predicted targets included genes involved in the regulation of tau and amyloid pathways in AD like MAPT, BACE1 and mTOR.

Author(s): 
Denk, Johannes
Boelmans, Kai
Siegismund, Christine
Lassner, Dirk
Arlt, Sˆnke
Jahn, Holger
Item Type: 
Journal Article
Publication Title: 
PloS One
Journal Abbreviation: 
PLoS ONE
Publication Date: 
2015
Publication Year: 
2015
Pages: 
e0126423
Volume: 
10
Issue: 
5
ISSN: 
1932-6203
DOI: 
10.1371/journal.pone.0126423
Library Catalog: 
PubMed
Extra: 
PMID: 25992776 PMCID: PMC4439119

Turabian/Chicago Citation

Johannes Denk, Kai Boelmans, Christine Siegismund, Dirk Lassner, Sˆnke Arlt and Holger Jahn. 2015. "MicroRNA Profiling of CSF Reveals Potential Biomarkers to Detect Alzheimer`s Disease." PloS One 10: 5: e0126423. 10.1371/journal.pone.0126423.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1371/journal.pone.0126423 | issn = 1932-6203 | volume = 10 | pages = e0126423 | last = Denk | first = Johannes | coauthors = Boelmans, Kai, Siegismund, Christine, Lassner, Dirk, Arlt, Sˆnke, Jahn, Holger | title = MicroRNA Profiling of CSF Reveals Potential Biomarkers to Detect Alzheimer`s Disease | journal = PloS One | date = 2015 | pmid = | pmc = }} </ref>