Identification of miRNAs as Potential Biomarkers in Cerebrospinal Fluid from Amyotrophic Lateral Sclerosis Patients
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disorder. Since no diagnostic laboratory test exists, the identification of specific biomarkers could be fundamental in clinical practice. microRNAs (miRNAs) are considered promising biomarkers for neurodegenerative diseases. The aim of the study was to identify a CSF miRNA set that could differentiate ALS from non-ALS condition. miRNA profiling in CSF from ALS patients (n = 24; eight with C9orf72 expansion) and unaffected control subjects (n = 24) by quantitative reverse transcription PCR identified fourteen deregulated miRNAs. Validation experiments confirmed eight miRNAs as significantly deregulated in ALS. No significant differences were observed between ALS patients with or without C9orf72 expansion. The receiver operator characteristic (ROC) curve analyses revealed the highest diagnostic accuracy for the upregulated miR181a-5p and the downregulated miR21-5p and miR15b-5p. The miR181a-5p/miR21-5p and miR181a-5p/miR15b-5p ratios detected ALS with 90 and 85 % sensitivity and 87 and 91 % specificity, respectively, confirming the application potential as disease biomarkers. These deregulated miRNAs are implicated in apoptotic way and provide insight into processes responsible for motor neuron degeneration.
KeywordsAmyotrophic lateral sclerosis Cerebrospinal fluid microRNA C9orf72 expansion Biomarkers
The authors thank Dr. Donatella Moschettini for providing CSF samples from control subjects and Dr. Marisa Carone for help in collecting clinical data. AAC and AJ thank the Motor Neurone Disease Association and the ALS Association for support.
The work leading up to this publication was funded by the European Community’s Health Seventh Framework Programme (FP7/2007–2013; Grant Agreement Number 259867) (AAC) and by the Associazione Polisportiva Torrenieri a.s.d.- Ice Bucket Challenge (2268-2014-BS-CONTRLIB_001) (SB). MB was supported by a doctoral Fellowship award from the Dottorato Toscano in Neuroscienze.
Compliance with Ethical Standards
Conflict of interest
This is an EU Joint Programme—Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organizations under the aegis of JPND—www.jpnd.eu (United Kingdom, Medical Research Council and Economic and Social Research Council). AAC receives salary support from the National Institute for Health Research (NIHR) Dementia Biomedical Research Unit and Biomedical Research Centre in Mental Health at South London and Maudsley NHS Foundation Trust and King’s College Hospital. All the other authors do not have any conflict of interest.
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