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.
Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
Michele
M
Benigni
Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy. claudia.ricci@unisi.it.
Claudia
C
Ricci
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Ashley R
AR
Jones
Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
Fabio
F
Giannini
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Ammar
A
Al-Chalabi
Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
Stefania
S
Battistini
D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D003937:Diagnosis, Differential; D006801:Humans; D035683:MicroRNAs / Q000134:cerebrospinal fluid*; D060888:Real-Time Polymerase Chain Reaction
D015415:Biomarkers; D035683:MicroRNAs
Amyotrophic lateral sclerosis; Biomarkers; C9orf72 expansion; Cerebrospinal fluid; microRNA