dc.contributor.author |
Ryan, Brigid |
en |
dc.contributor.author |
Williams, Joanna M |
en |
dc.contributor.author |
Curtis, Maurice |
en |
dc.date.accessioned |
2020-07-07T02:20:55Z |
en |
dc.date.issued |
2019-07 |
en |
dc.identifier.issn |
0306-4522 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/51923 |
en |
dc.description.abstract |
Pathological accumulation of tau protein in brain cells is the hallmark of a group of neurodegenerative diseases called tauopathies. Accumulation of tau protein begins years before the onset of symptoms, which include deficits in cognition, behavior and movement. The pre-symptomatic phase of tauopathy may be the best time to deliver disease-modifying treatments, but this is only possible if prognostic, pre-symptomatic biomarkers are identified. Here we describe the profiling of blood plasma microRNAs in a mouse model of tauopathy, in order to identify biomarkers of pre-symptomatic tauopathy. Circulating RNAs were isolated from blood plasma of 16-week-old and 53-week-old hTau mice and age-matched wild type controls (n = 28). Global microRNA profiling was performed using small RNA sequencing (Illumina) and selected microRNAs were validated using individual TaqMan RT-qPCR. The area under the receiver operating characteristic curve (AUC) was used to evaluate discriminative accuracy. We identified three microRNAs (miR-150-5p, miR-155-5p, miR-375-3p) that were down-regulated in 16-week-old hTau mice, which do not yet exhibit a behavioral phenotype and therefore represent pre-symptomatic tauopathy. The discriminative accuracy was AUC 0.98, 0.95 and 1, respectively. Down-regulation of these microRNAs persisted at 53 weeks of age, when hTau mice exhibit cognitive deficits and advanced neuropathology. Bioinformatic analysis showed that these three microRNAs converge on pathways associated with neuronal signaling and phosphorylation of tau. Thus, these circulating microRNAs appear to reflect neuropathological change and are promising candidates in the development of biomarkers of pre-symptomatic tauopathy. |
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dc.format.medium |
Print-Electronic |
en |
dc.language |
eng |
en |
dc.relation.ispartofseries |
Neuroscience |
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dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
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dc.subject |
Animals |
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dc.subject |
Mice, Transgenic |
en |
dc.subject |
Mice |
en |
dc.subject |
Tauopathies |
en |
dc.subject |
Disease Models, Animal |
en |
dc.subject |
tau Proteins |
en |
dc.subject |
MicroRNAs |
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dc.subject |
Gene Expression Profiling |
en |
dc.subject |
Down-Regulation |
en |
dc.subject |
Male |
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dc.subject |
Biomarkers |
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dc.title |
Plasma MicroRNAs Are Altered Early and Consistently in a Mouse Model of Tauopathy. |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.neuroscience.2019.05.036 |
en |
pubs.begin-page |
164 |
en |
pubs.volume |
411 |
en |
dc.rights.holder |
Copyright: The author |
en |
pubs.end-page |
176 |
en |
pubs.publication-status |
Published |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Research Support, Non-U.S. Gov't |
en |
pubs.subtype |
Journal Article |
en |
pubs.elements-id |
775792 |
en |
pubs.org-id |
Medical and Health Sciences |
en |
pubs.org-id |
Medical Sciences |
en |
pubs.org-id |
Anatomy and Medical Imaging |
en |
dc.identifier.eissn |
1873-7544 |
en |
pubs.record-created-at-source-date |
2019-06-02 |
en |
pubs.dimensions-id |
31152932 |
en |