Cited by 236MicroRNA in disease regulationAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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MicroRNA Profiling of CSF Reveals Potential Biomarkers to Detect Alzheimer`s Disease

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Denk, Johannes, Boelmans, Kai, Siegismund, Christine, Lassner, Dirk, Arlt, Sönke, Jahn, Holger·2015·PLOS ONE

DOI 10.1371/journal.pone.0126423PMC PMC4439119

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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.

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Additional file 5 of MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration
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Additional file 2 of MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration
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Additional file 3 of MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration
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Additional file 4 of MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration
Wallach, T., Mossmann, Z. J., Szczepek, M., Wetzel, M., Machado, R. S. R., Raden, M., Miladi, M., Kleinau, G., Krüger, C., Dembny, P., et al. (2021) · Figshare · doi:10.6084/m9.figshare.17088335
Additional file 8 of MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration
Wallach, T., Mossmann, Z. J., Szczepek, M., Wetzel, M., Machado, R. S. R., Raden, M., Miladi, M., Kleinau, G., Krüger, C., Dembny, P., et al. (2021) · Figshare · doi:10.6084/m9.figshare.17088347
Additional file 11 of MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration
Wallach, T., Mossmann, Z. J., Szczepek, M., Wetzel, M., Machado, R. S. R., Raden, M., Miladi, M., Kleinau, G., Krüger, C., Dembny, P., et al. (2021) · Figshare · doi:10.6084/m9.figshare.17088317
Additional file 13 of MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration
Wallach, T., Mossmann, Z. J., Szczepek, M., Wetzel, M., Machado, R. S. R., Raden, M., Miladi, M., Kleinau, G., Krüger, C., Dembny, P., et al. (2021) · Figshare · doi:10.6084/m9.figshare.17088323
Additional file 6 of MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration
Wallach, T., Mossmann, Z. J., Szczepek, M., Wetzel, M., Machado, R. S. R., Raden, M., Miladi, M., Kleinau, G., Krüger, C., Dembny, P., et al. (2021) · Figshare · doi:10.6084/m9.figshare.17088341
Additional file 1 of MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration
Wallach, T., Mossmann, Z. J., Szczepek, M., Wetzel, M., Machado, R. S. R., Raden, M., Miladi, M., Kleinau, G., Krüger, C., Dembny, P., et al. (2021) · Figshare · doi:10.6084/m9.figshare.17088326
Additional file 10 of MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration
Wallach, T., Mossmann, Z. J., Szczepek, M., Wetzel, M., Machado, R. S. R., Raden, M., Miladi, M., Kleinau, G., Krüger, C., Dembny, P., et al. (2021) · Figshare · doi:10.6084/m9.figshare.17088314
Additional file 9 of MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration
Wallach, T., Mossmann, Z. J., Szczepek, M., Wetzel, M., Machado, R. S. R., Raden, M., Miladi, M., Kleinau, G., Krüger, C., Dembny, P., et al. (2021) · Figshare · doi:10.6084/m9.figshare.17088350
Additional file 2 of Prediction of P-tau/Aβ42 in the cerebrospinal fluid with blood microRNAs in Alzheimer’s disease
Jia, L., Zhu, M., Yang, J., Pang, Y., Wang, Q., Li, Y., Li, T., Li, F., Wang, Q., Li, Y., et al. (2021) · Figshare · doi:10.6084/m9.figshare.17010112
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Authors: Denk, J., Boelmans, K., Siegismund, C., Lassner, D., Arlt, S., & Jahn, H.
Affiliations: University Medical Center Hamburg-Eppendorf (DE)
Institut Kardiale Diagnostik und Therapie (DE)
Corresponding author: Jahn, Holger
ORCID: Denk, Johannes
Siegismund, Christine
Lassner, Dirk
Arlt, Sönke
Jahn, Holger
Venue: PLOS ONE
Publisher: Public Library of Science (PLoS)
Published: 2015-05-20
Volume: 10
Issue: 5
Pages: e0126423
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0126423
PMC: PMC4439119
OpenAlex: W1487838396
Cited by: 236
References: 77
Citations by year: 2026: 5 · 2025: 11 · 2024: 15 · 2023: 15 · 2022: 18 · 2021: 44 · 2020: 22 · 2019: 24 · 2018: 24 · 2017: 30 · 2016: 21 · 2015: 7
FWCI: 9.04
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: Alzheimer's disease, miRNA expression profiling, cerebrospinal fluid, biomarkers, miR-100, miR-103, miR-375, miR-146a, microRNA expression, OpenArray, disease diagnosis, MAPT, BACE1, mTOR
MeSH terms: Aged, Alzheimer Disease, Female, Humans, Male, Middle Aged, Signal Transduction, Biomarkers, Discriminant Analysis, Aspartic Acid Endopeptidases, tau Proteins, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, MicroRNAs, Epigenesis, Genetic, Amyloid Precursor Protein Secretases, TOR Serine-Threonine Kinases

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MicroRNA Profiling of CSF Reveals Potential Biomarkers to Detect Alzheimer`s Disease

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