Circulating miRNA Biomarkers for Alzheimer's Disease
Open Access
- 29 July 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (7), e69807
- https://doi.org/10.1371/journal.pone.0069807
Abstract
A minimally invasive diagnostic assay for early detection of Alzheimer's disease (AD) is required to select optimal patient groups in clinical trials, monitor disease progression and response to treatment, and to better plan patient clinical care. Blood is an attractive source for biomarkers due to minimal discomfort to the patient, encouraging greater compliance in clinical trials and frequent testing. MiRNAs belong to the class of non-coding regulatory RNA molecules of ∼22 nt length and are now recognized to regulate ∼60% of all known genes through post-transcriptional gene silencing (RNAi). They have potential as useful biomarkers for clinical use because of their stability and ease of detection in many tissues, especially blood. Circulating profiles of miRNAs have been shown to discriminate different tumor types, indicate staging and progression of the disease and to be useful as prognostic markers. Recently their role in neurodegenerative diseases, both as diagnostic biomarkers as well as explaining basic disease etiology has come into focus. Here we report the discovery and validation of a unique circulating 7-miRNA signature (hsa-let-7d-5p, hsa-let-7g-5p, hsa-miR-15b-5p, hsa-miR-142-3p, hsa-miR-191-5p, hsa-miR-301a-3p and hsa-miR-545-3p) in plasma, which could distinguish AD patients from normal controls (NC) with >95% accuracy (AUC of 0.953). There was a >2 fold difference for all signature miRNAs between the AD and NC samples, with p-values<0.05. Pathway analysis, taking into account enriched target mRNAs for these signature miRNAs was also carried out, suggesting that the disturbance of multiple enzymatic pathways including lipid metabolism could play a role in AD etiology.Keywords
This publication has 99 references indexed in Scilit:
- Blood serum miRNA: Non-invasive biomarkers for Alzheimer's diseaseExperimental Neurology, 2012
- MicroRNA dysregulation in colorectal cancer: a clinical perspectiveBritish Journal of Cancer, 2011
- Identifying and validating biomarkers for Alzheimer's diseaseTrends in Biotechnology, 2011
- MicroRNA-101 downregulates Alzheimer’s amyloid-β precursor protein levels in human cell cultures and is differentially expressedBiochemical and Biophysical Research Communications, 2010
- Mammalian microRNAs predominantly act to decrease target mRNA levelsNature, 2010
- Early detection of lung adenocarcinoma in sputum by a panel of microRNA markersInternational Journal of Cancer, 2010
- The effects of normal aging and ApoE genotype on the levels of CSF biomarkers for Alzheimer's diseaseNeurobiology of Aging, 2009
- Axon guidance and synaptic maintenance: preclinical markers for neurodegenerative disease and therapeuticsTrends in Neurosciences, 2009
- A Mammalian microRNA Expression Atlas Based on Small RNA Library SequencingCell, 2007
- Global prevalence of dementia: a Delphi consensus studyThe Lancet, 2005