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MicroRNA Profiling of CSF Reveals Potential Biomarkers to Detect Alzheimer`s Disease
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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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“However, there has been a lack of consistent findings among CSF microRNAs studies.”
From Intra- and Inter-individual Variability of microRNA Levels in Human Cerebrospinal Fluid: Critical Implications for Biomarker Discovery (2017) · cites this paper as [12]
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Metadata
- 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
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-05-20
- Volume
- 10
- Issue
- 5
- Pages
- e0126423
- ISSN
- 1932-6203 (ISSN-L)
- 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
- 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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