title: Disease-related changes in the cerebrospinal fluid metabolome in amyotrophic lateral sclerosis detected by GC/TOFMS.
abstract: OBJECTIVE
  The changes in the cerebrospinal fluid (CSF) metabolome associated with the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are poorly understood and earlier smaller studies have shown conflicting results. The metabolomic methodology is suitable for screening large cohorts of samples. Global metabolomics can be used for detecting changes of metabolite concentrations in samples of fluids such as CSF.
  
  
  METHODS
  Using gas chromatography coupled to mass spectrometry (GC/TOFMS) and multivariate statistical modeling, we simultaneously studied the metabolome signature of ∼120 small metabolites in the CSF of patients with ALS, stratified according to hereditary disposition and clinical subtypes of ALS in relation to controls.
  
  
  RESULTS
  The study is the first to report data validated over two sub-sets of ALS vs. control patients for a large set of metabolites analyzed by GC/TOFMS. We find that patients with sporadic amyotrophic lateral sclerosis (SALS) have a heterogeneous metabolite signature in the cerebrospinal fluid, in some patients being almost identical to controls. However, familial amyotrophic lateral sclerosis (FALS) without superoxide dismutase-1 gene (SOD1) mutation is less heterogeneous than SALS. The metabolome of the cerebrospinal fluid of 17 ALS patients with a SOD1 gene mutation was found to form a separate homogeneous group. Analysis of metabolites revealed that glutamate and glutamine were reduced, in particular in patients with a familial predisposition. There are significant differences in the metabolite profile and composition among patients with FALS, SALS and patients carrying a mutation in the SOD1 gene suggesting that the neurodegenerative process in different subtypes of ALS may be partially dissimilar.
  
  
  CONCLUSIONS
  Patients with a genetic predisposition to amyotrophic lateral sclerosis have a more distinct and homogeneous signature than patients with a sporadic disease.
authors.affiliation: Institute of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Wuolikainen
authors.forename: Thomas
authors.initials: T
authors.lastname: Moritz
authors.forename: Stefan L
authors.initials: SL
authors.lastname: Marklund
authors.forename: Henrik
authors.initials: H
authors.lastname: Antti
authors.forename: Peter Munch
authors.initials: PM
authors.lastname: Andersen
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D005838:Genotype; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D009154:Mutation; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1