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  Specific serum and CSF microRNA profiles distinguish sporadic behavioural variant of frontotemporal dementia compared with Alzheimer patients and cognitively healthy controls

Denk, J., Oberhauser, F., Kornhuber, J., Wiltfang, J., Fassbender, K., Schroeter, M. L., et al. (2018). Specific serum and CSF microRNA profiles distinguish sporadic behavioural variant of frontotemporal dementia compared with Alzheimer patients and cognitively healthy controls. PLoS One, 13(5): e0197329. doi:10.1371/journal.pone.0197329.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0001-F6DE-0 Version Permalink: https://hdl.handle.net/21.11116/0000-0003-A5A7-6
Genre: Journal Article

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 Creators:
Denk , Johannes 1, Author
Oberhauser, Felix1, Author
Kornhuber, Johannes 2, Author
Wiltfang, Jens 3, Author
Fassbender, Klaus 4, Author
Schroeter, Matthias L.5, 6, Author           
Volk, Alexander E. 7, Author
Diehl-Schmid, Janine 8, Author
Prudlo , Johannes 9, Author
Danek, Adrian 10, Author
Landwehrmeyer, Bernhard 11, Author
Lauer, Martin 12, Author
Otto, Markus 11, Author
Jahn, Holger 1, 13, Author
Affiliations:
1Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Germany, ou_persistent22              
2Department of Psychology and Psychotherapy, Friedrich Alexander University Erlangen, Germany, ou_persistent22              
3Department of Psychiatry and Psychotherapy, Georg August University, Göttingen, Germany, ou_persistent22              
4Department of Neurology, Saarland University Homburg, Germany, ou_persistent22              
5Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, Leipzig, DE, ou_634549              
6Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              
7Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Germany, ou_persistent22              
8Department of Psychiatry and Psychotherapy, TU Munich, Germany, ou_persistent22              
9Department of Neurology, University Medicine Rostock, Germany, ou_persistent22              
10Department of Neurology, Ludwig Maximilians University Munich, Germany, ou_persistent22              
11Department of Neurology, Ulm University, Germany, ou_persistent22              
12Clinic for Psychiatry, Psychosomatic Medicine and Psychotherapy, Julius Maximilian University, Würzburg, Germany, ou_persistent22              
13AMEOS Klinikum Heiligenhafen, Germany, ou_persistent22              

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 Abstract: Information on circulating miRNAs in frontotemporal lobar degeneration is very limited and conflicting results have complicated an interpretation in Alzheimer's disease thus far. In the present study we I) collected samples from multiple clinical centers across Germany, II) defined 3 homogenous patient groups with high sample sizes (bvFTD n = 48, AD n = 48 and cognitively healthy controls n = 44), III) compared expression levels in both CSF and serum samples and IV) detected a limited set of miRNAs by using a MIQE compliant protocol based on SYBR-green miRCURY assays that have proven reliable to generate reproducible results. We included several quality controls that identified and reduced technical variation to increase the reliability of our data. We showed that the expression levels of circulating miRNAs measured in CSF did not correlate with levels in serum. Using cluster analysis we found expression pattern in serum that, in part, reflects the genomic organization and affiliation to a specific miRNA family and that were specifically altered in bvFTD, AD, and control groups. Applying factor analysis we identified a 3-factor model characterized by a miRNA signature that explained 80% of the variance classifying healthy controls with 97%, bvFTD with 77% and AD with 72% accuracy. MANOVA confirmed signals like miR-320a and miR-26b-5p at BH corrected significance that contributed most to discriminate bvFTD cases with 96% sensitivity and 90% specificity and AD cases with 89% sensitivity and specificity compared to healthy controls, respectively. Correlation analysis revealed that miRNAs from the 3-factor model also correlated with levels of protein biomarker amyloid-beta1-42 and phosphorylated neurofilament heavy chain, indicating their potential role in the monitoring of progressive neuronal degeneration. Our data show that miRNAs can be reproducibly measured in serum and CSF without pre-amplification and that serum includes higher expressed signals that demonstrate an overall better ability to classify bvFTD, AD and healthy controls compared to signals detected in CSF.

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Language(s): eng - English
 Dates: 2018-02-142018-04-292018-05-10
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1371/journal.pone.0197329
PMID: 29746584
PMC: PMC5945001
Other: eCollection 2018
 Degree: -

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Project name : German Consortium for Frontotemporal Lobar Degeneration
Grant ID : O1GI1007A
Funding program : -
Funding organization : German Federal Ministry of Education and Research (BMBF)
Project name : PreFrontAls
Grant ID : -
Funding program : -
Funding organization : Joint Programme – Neurodegenerative Disease Research (JPND)
Project name : Conservative iron chelation as a disease-modifying strategy in Parkinson’s disease: a multicentric, parallel-group, placebo-controlled, randomized clinical trial of deferiprone / FAIR-PARK II
Grant ID : 633190
Funding program : Horizon 2020
Funding organization : European Commission (EC)
Project name : Nutzung des menschlichen Peptidoms für die Entwicklung neuer antimikrobieller und anti-Krebs Therapeutika / SFB 1279
Grant ID : -
Funding program : -
Funding organization : German Research Foundation (DFG)
Project name : -
Grant ID : D.3830
Funding program : -
Funding organization : Foundation of the State Baden-Württemberg
Project name : -
Grant ID : D.5009
Funding program : -
Funding organization : Boehringer Ingelheim Ulm University BioCenter
Project name : -
Grant ID : -
Funding program : -
Funding organization : Thierry Latran Foundation
Project name : -
Grant ID : VO 2028/1-1
Funding program : -
Funding organization : Deutsche Forschungsgemeinschaft (DFG)

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Title: PLoS One
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 13 (5) Sequence Number: e0197329 Start / End Page: - Identifier: ISSN: 1932-6203
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000277850