title: Metabolomics in cerebrospinal fluid of patients with amyotrophic lateral sclerosis: an untargeted approach via high-resolution mass spectrometry.
abstract: Amyotrophic lateral sclerosis (ALS) is characterized by the absence of reliable diagnostic biomarkers. The aim of the study was to (i) devise an untargeted metabolomics methodology that reliably compares cerebrospinal fluid (CSF) from ALS patients and controls by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS); (ii) ascertain a metabolic signature of ALS by use of the LC-HRMS platform; (iii) identify metabolites for use as diagnostic or pathophysiologic markers. We developed a method to analyze CSF components by UPLC coupled with a Q-Exactive mass spectrometer that uses electrospray ionization. Metabolomic profiles were created from the CSF obtained at diagnosis from ALS patients and patients with other neurological conditions. We performed multivariate analyses (OPLS-DA) and univariate analyses to assess the contribution of individual metabolites as well as compounds identified in other studies. Sixty-six CSF samples from ALS patients and 128 from controls were analyzed. Metabolome analysis correctly predicted the diagnosis of ALS in more than 80% of cases. OPLS-DA identified four features that discriminated diagnostic group (p < 0.004). Our data demonstrate that untargeted metabolomics with LC-HRMS is a robust procedure to generate a specific metabolic profile for ALS from CSF and could be an important aid to the development of biomarkers for the disease.
authors.affiliation: Unité 930, Institut National de la Santé et de la Recherche Médicale, 37044 Tours, France. helene.blasco@univ-tours.fr
authors.forename: Hélène
authors.initials: H
authors.lastname: Blasco
authors.forename: Philippe
authors.initials: P
authors.lastname: Corcia
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Pradat
authors.forename: Cinzia
authors.initials: C
authors.lastname: Bocca
authors.forename: Paul H
authors.initials: PH
authors.lastname: Gordon
authors.forename: Charlotte
authors.initials: C
authors.lastname: Veyrat-Durebex
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mavel
authors.forename: Lydie
authors.initials: L
authors.lastname: Nadal-Desbarats
authors.forename: Caroline
authors.initials: C
authors.lastname: Moreau
authors.forename: David
authors.initials: D
authors.lastname: Devos
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
authors.forename: Patrick
authors.initials: P
authors.lastname: Emond
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D000704:Analysis of Variance; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: D015415:Biomarkers