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Cerebrospinal Fluid MicroRNA Profiling Using Quantitative Real Time PCR
Published on: January 22, 2014
Circulating microRNAs as Biomarkers of Alzheimer's Disease: A Systematic Review
Helen Zong Ying Wu1,2, Kwok Leung Ong3, Katrin Seeher1,2
1Centre for Healthy Brain and Ageing, School of Psychiatry, UNSW, Sydney, Australia.
Background:
In recent years, microRNAs (miRNA), a class of non-coding RNA known to regulate protein expression post-transcriptionally, have been recognized as novel biomarkers of diseases.
Objective:
In this systematic review, we identify miRNAs that are differentially expressed in Alzheimer's disease (AD) and/or mild cognitive impairment (MCI) and evaluate their accuracy as potential blood biomarkers.
Methods:
Eligible studies of miRNAs in peripheral blood distinguishing patients with AD or MCI from cognitively normal controls were identified through standardized search strategies in Medline, PubMed, and Embase. MiRNAs that were differentially expressed were identified and where available their sensitivity and specificity for AD or MCI extracted from the retrieved studies.
Results:
Eighteen studies investigated the diagnostic value of miRNAs as peripheral biomarkers of AD/MCI. Twenty miRNAs were significantly upregulated and 32 miRNAs downregulated in AD compared to controls in ten AD studies. Nine miRNAs were consistently dysregulated in more than one study. Of the 8 MCI studies, only one miRNA, miR-132, was consistently upregulated in three independent studies. Of the studies that reported diagnostic accuracy data, the majority of miRNA panels and individual miRNAs had a sensitivity and specificity greater than 0.75.
Conclusion:
Individual studies suggest that miRNAs can differentiate patients with AD/MCI from cognitively normal controls with modest accuracy. However, the literature is constrained by methodological differences between studies, with few studies assessing the same miRNAs. To become potential biomarkers for AD, further studies with standardized study designs for replication and validation are required. Results from this review may help researchers select candidate miRNAs for further investigation.
Insights
MicroRNAs (miRNAs) show potential as blood biomarkers for Alzheimer's disease (AD) and mild cognitive impairment (MCI). While some miRNAs are differentially expressed, further standardized research is needed for validation as reliable diagnostic tools.
Area of Science:
- Biomarkers
- Neuroscience
- Molecular Biology
Background:
- MicroRNAs (miRNAs) are non-coding RNAs regulating gene expression.
- miRNAs are emerging as potential disease biomarkers.
- Their role in Alzheimer's disease (AD) and mild cognitive impairment (MCI) is under investigation.
Purpose of the Study:
- To systematically review miRNAs differentially expressed in AD and/or MCI.
- To evaluate the diagnostic accuracy of these miRNAs as blood biomarkers.
Main Methods:
- Systematic search of Medline, PubMed, and Embase databases.
- Identification of differentially expressed miRNAs in peripheral blood of AD/MCI patients versus controls.
- Extraction of sensitivity and specificity data for diagnostic accuracy.
Main Results:
- Eighteen studies examined miRNA diagnostic value.
- Twenty miRNAs upregulated and 32 downregulated in AD; nine consistently dysregulated.
- miR-132 consistently upregulated in three MCI studies; most biomarkers showed >0.75 sensitivity/specificity.
Conclusions:
- miRNAs show modest accuracy in differentiating AD/MCI patients from controls.
- Methodological heterogeneity and limited miRNA assessment hinder current validation.
- Standardized study designs are crucial for validating miRNAs as reliable AD biomarkers.

