Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls
Abstract 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 compa...
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| Format: | Article |
| Language: | English |
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BMC
2020-05-01
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| Series: | Alzheimer’s Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13195-020-00627-0 |
| _version_ | 1818048878006501376 |
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| author | Helen Zong Ying Wu Anbupalam Thalamuthu Lesley Cheng Christopher Fowler Colin L. Masters Perminder Sachdev Karen A. Mather and the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing |
| author_facet | Helen Zong Ying Wu Anbupalam Thalamuthu Lesley Cheng Christopher Fowler Colin L. Masters Perminder Sachdev Karen A. Mather and the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing |
| author_sort | Helen Zong Ying Wu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-10T10:28:40Z |
| format | Article |
| id | doaj.art-09fa4bac527946bd83a99fb2fcbb9904 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-12-10T10:28:40Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-09fa4bac527946bd83a99fb2fcbb99042022-12-22T01:52:38ZengBMCAlzheimer’s Research & Therapy1758-91932020-05-0112111110.1186/s13195-020-00627-0Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controlsHelen Zong Ying Wu0Anbupalam Thalamuthu1Lesley Cheng2Christopher Fowler3Colin L. Masters4Perminder Sachdev5Karen A. Mather6and the Australian Imaging Biomarkers and Lifestyle Flagship Study of AgeingCentre for Healthy Brain and Ageing, University of New South WalesCentre for Healthy Brain and Ageing, University of New South WalesDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe UniversityFlorey Institute, University of MelbourneFlorey Institute, University of MelbourneCentre for Healthy Brain and Ageing, University of New South WalesCentre for Healthy Brain and Ageing, University of New South WalesAbstract 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.http://link.springer.com/article/10.1186/s13195-020-00627-0Alzheimer’s diseaseBiomarkerMicroRNAAmyloid imagingEarly diagnosis |
| spellingShingle | Helen Zong Ying Wu Anbupalam Thalamuthu Lesley Cheng Christopher Fowler Colin L. Masters Perminder Sachdev Karen A. Mather and the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer’s disease and controls Alzheimer’s Research & Therapy Alzheimer’s disease Biomarker MicroRNA Amyloid imaging Early diagnosis |
| 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 | Alzheimer’s disease Biomarker MicroRNA Amyloid imaging Early diagnosis |
| url | http://link.springer.com/article/10.1186/s13195-020-00627-0 |
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