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Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer's disease and controls
Helen Zong Ying Wu1,2, Anbupalam Thalamuthu3,4, Lesley Cheng5
1Centre for Healthy Brain and Ageing, University of New South Wales, Sydney, Australia. Helen.Wu@health.nsw.gov.au.
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.
Insights
Two specific microRNAs (miRNAs) in blood, miR-146b-5p and miR-15b-5p, show consistent differences in expression in Alzheimer's disease (AD) patients compared to controls, suggesting potential as Alzheimer's biomarkers.
Area of Science:
- Neuroscience
- Genetics
- Biomarker Discovery
Background:
- Peripheral blood microRNAs (miRNAs) are explored as potential Alzheimer's disease (AD) biomarkers.
- Previous studies yielded inconsistent results due to sample heterogeneity.
- This study aims to identify reliable blood miRNA biomarkers for AD.
Purpose of the Study:
- To establish candidate blood miRNA biomarkers for AD.
- To compare miRNA expression between individuals with brain amyloid-defined AD and cognitively normal controls.
Main Methods:
- Small RNA sequencing of blood samples from 71 participants (40 AD, 31 controls) from the Australian Imaging Biomarkers Lifestyle Study of Ageing (AIBL) cohort.
- Differential expression analysis using Fisher's exact tests.
- Replication using a public AD blood miRNA dataset and in silico analysis of miRNA targets.
Main Results:
- 816 miRNAs were analyzed; 71 showed significant differential expression between AD and control groups (p < 0.05).
- miR-146b-5p and miR-15b-5p were consistently significant in both the primary and replication cohorts.
- Pathway analysis indicated involvement in the innate immune system and cell cycle regulation, relevant to AD pathogenesis.
Conclusions:
- Blood miR-146b-5p and miR-15b-5p demonstrate consistent differential expression in AD patients.
- Further validation in well-characterized cohorts is necessary to establish their clinical utility as AD biomarkers.
