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Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls

BACKGROUND: Peripheral blood microRNAs (miRNA) have been identified as potential biomarkers for Alzheimer’s disease (AD). Study results have generally been inconsistent and limited by sample heterogeneity. The aim of this study is to establish candidate blood miRNA biomarkers for AD by comparing dif...

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Autores principales: Wu, Helen Zong Ying, Thalamuthu, Anbupalam, Cheng, Lesley, Fowler, Christopher, Masters, Colin L., Sachdev, Perminder, Mather, Karen A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229622/
https://www.ncbi.nlm.nih.gov/pubmed/32414413
http://dx.doi.org/10.1186/s13195-020-00627-0
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author Wu, Helen Zong Ying
Thalamuthu, Anbupalam
Cheng, Lesley
Fowler, Christopher
Masters, Colin L.
Sachdev, Perminder
Mather, Karen A.
author_facet Wu, Helen Zong Ying
Thalamuthu, Anbupalam
Cheng, Lesley
Fowler, Christopher
Masters, Colin L.
Sachdev, Perminder
Mather, Karen A.
author_sort Wu, Helen Zong Ying
collection PubMed
description BACKGROUND: Peripheral blood microRNAs (miRNA) have been identified as potential biomarkers for Alzheimer’s disease (AD). Study results have generally been inconsistent and limited by sample heterogeneity. The aim of this study is to establish candidate blood miRNA biomarkers for AD by comparing differences in miRNA expression between participants with brain amyloid imaging-defined AD and normal cognition. METHODS: Blood RNA was extracted from a subset of participants from the Australian Imaging Biomarkers Lifestyle Study of Ageing cohort (AIBL) with brain amyloid imaging results. MiRNA profiling was performed using small RNA sequencing on 71 participants, comprising 40 AD with high brain amyloid burden on imaging (amyloid positive) and 31 cognitively normal controls with low brain amyloid burden (amyloid negative). Cross-sectional comparisons were made between groups to examine differential miRNA expression levels using Fisher’s exact tests. Replication of results was undertaken using a publicly available dataset of blood miRNA data of AD and controls. In silico analysis of downstream messenger RNA targets of candidate miRNAs was performed to elucidate potential biological function. RESULTS: After quality control, 816 miRNAs were available for analysis. There were 71 significantly differentially expressed miRNAs between the AD and control groups (p < 0.05). Two of these miRNAs, miR-146b-5p and miR-15b-5p, were also significant in the replication cohort. Pathways analysis showed these miRNAs to be involved in innate immune system and regulation of the cell cycle, respectively, both of which have relevance to AD pathogenesis. CONCLUSION: Blood miR-146b-5p and miR15b-5p showed consistent differential expression in AD compared to controls. Further replication and translational studies in strictly phenotyped cohorts are needed to establish their role as biomarkers for AD to have clinical utility.
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spelling pubmed-72296222020-05-27 Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls Wu, Helen Zong Ying Thalamuthu, Anbupalam Cheng, Lesley Fowler, Christopher Masters, Colin L. Sachdev, Perminder Mather, Karen A. Alzheimers Res Ther Research BACKGROUND: Peripheral blood microRNAs (miRNA) have been identified as potential biomarkers for Alzheimer’s disease (AD). Study results have generally been inconsistent and limited by sample heterogeneity. The aim of this study is to establish candidate blood miRNA biomarkers for AD by comparing differences in miRNA expression between participants with brain amyloid imaging-defined AD and normal cognition. METHODS: Blood RNA was extracted from a subset of participants from the Australian Imaging Biomarkers Lifestyle Study of Ageing cohort (AIBL) with brain amyloid imaging results. MiRNA profiling was performed using small RNA sequencing on 71 participants, comprising 40 AD with high brain amyloid burden on imaging (amyloid positive) and 31 cognitively normal controls with low brain amyloid burden (amyloid negative). Cross-sectional comparisons were made between groups to examine differential miRNA expression levels using Fisher’s exact tests. Replication of results was undertaken using a publicly available dataset of blood miRNA data of AD and controls. In silico analysis of downstream messenger RNA targets of candidate miRNAs was performed to elucidate potential biological function. RESULTS: After quality control, 816 miRNAs were available for analysis. There were 71 significantly differentially expressed miRNAs between the AD and control groups (p < 0.05). Two of these miRNAs, miR-146b-5p and miR-15b-5p, were also significant in the replication cohort. Pathways analysis showed these miRNAs to be involved in innate immune system and regulation of the cell cycle, respectively, both of which have relevance to AD pathogenesis. CONCLUSION: Blood miR-146b-5p and miR15b-5p showed consistent differential expression in AD compared to controls. Further replication and translational studies in strictly phenotyped cohorts are needed to establish their role as biomarkers for AD to have clinical utility. BioMed Central 2020-05-15 /pmc/articles/PMC7229622/ /pubmed/32414413 http://dx.doi.org/10.1186/s13195-020-00627-0 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Wu, Helen Zong Ying
Thalamuthu, Anbupalam
Cheng, Lesley
Fowler, Christopher
Masters, Colin L.
Sachdev, Perminder
Mather, Karen A.
Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls
title Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls
title_full Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls
title_fullStr Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls
title_full_unstemmed Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls
title_short Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls
title_sort differential blood mirna expression in brain amyloid imaging-defined alzheimer’s disease and controls
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229622/
https://www.ncbi.nlm.nih.gov/pubmed/32414413
http://dx.doi.org/10.1186/s13195-020-00627-0
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