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Differential expression of microRNAs in Alzheimer's disease brain, blood, and cerebrospinal fluid
Petros Takousis1, Angélique Sadlon1, Jessica Schulz2
1Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, London, UK.
Introduction:
Several microRNAs (miRNAs) have been implicated in Alzheimer's disease pathogenesis, but the evidence from individual case-control studies remains inconclusive.
Methods:
A systematic literature review was performed, followed by standardized multistage data extraction, quality control, and meta-analyses on eligible data for brain, blood, and cerebrospinal fluid specimens. Results were compared with miRNAs reported in the abstracts of eligible studies or recent qualitative reviews to assess novelty.
Results:
Data from 147 independent data sets across 107 publications were quantitatively assessed in 461 meta-analyses. Twenty-five, five, and 32 miRNAs showed studywide significant differential expression (α < 1·08 × 10-4) in brain, cerebrospinal fluid, and blood-derived specimens, respectively, with 5 miRNAs showing differential expression in both brain and blood. Of these 57 miRNAs, 13 had not been reported in the abstracts of previous original or review articles.
Discussion:
Our systematic assessment of differential miRNA expression is the first of its kind in Alzheimer's disease and highlights several miRNAs of potential relevance.
Insights
This study analyzed microRNAs (miRNAs) in Alzheimer's disease, finding 57 differentially expressed miRNAs across brain and blood samples. Thirteen of these novel miRNAs were previously unreported, offering new insights into Alzheimer's disease pathogenesis.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- MicroRNAs (miRNAs) are increasingly recognized for their role in Alzheimer's disease (AD) pathogenesis.
- Existing evidence from individual studies is often inconclusive, necessitating a comprehensive analysis.
Purpose of the Study:
- To systematically assess differential microRNA expression in Alzheimer's disease using a large-scale meta-analysis.
- To identify novel microRNAs associated with AD pathogenesis across different biological specimens.
Main Methods:
- A systematic literature review and meta-analysis of 107 publications, encompassing 147 independent datasets.
- Quantitative assessment of differential microRNA expression in brain, blood, and cerebrospinal fluid specimens.
- Comparison of findings with previously reported miRNAs to identify novel candidates.
Main Results:
- 461 meta-analyses revealed 57 microRNAs with studywide significant differential expression (α < 1.08 × 10⁻⁴).
- Twenty-five miRNAs were significant in brain, five in cerebrospinal fluid, and 32 in blood.
- Five miRNAs showed differential expression in both brain and blood specimens.
- Thirteen of the 57 identified miRNAs had not been previously reported in original or review articles.
Conclusions:
- This systematic meta-analysis represents the first comprehensive assessment of differential miRNA expression in Alzheimer's disease.
- The study highlights several potentially relevant miRNAs, including 13 novel candidates, for further investigation into AD pathogenesis.