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Disease-Related Changes in the Cerebrospinal Fluid Metabolome in Amyotrophic Lateral Sclerosis Detected by GCTOFMS 英文参考文献.docVIP

Disease-Related Changes in the Cerebrospinal Fluid Metabolome in Amyotrophic Lateral Sclerosis Detected by GCTOFMS 英文参考文献.doc

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Disease-Related Changes in the Cerebrospinal Fluid Metabolome in Amyotrophic Lateral Sclerosis Detected by GCTOFMS 英文参考文献

Disease-RelatedChangesintheCerebrospinalFluid MetabolomeinAmyotrophicLateralSclerosisDetected byGC/TOFMS AnnaWuolikainen1,2,ThomasMoritz3,StefanL.Marklund4,HenrikAntti2,PeterMunchAndersen1* 1InstituteofPharmacologyandClinicalNeuroscience,Umea?University,Umea?,Sweden,2DepartmentofChemistry,ComputationalLifeScienceCluster,Umea?University, Umea?, Sweden, 3Department of Forest Genetics and Plant Physiology, Umea? Plant Science Centre, Swedish University of Agricultural Sciences, Umea?, Sweden, 4DepartmentofMedicalBiosciences,ClinicalChemistry,Umea? University,Umea?, Sweden Abstract Background/Aim:Thechangesinthecerebrospinalfluid(CSF)metabolomeassociatedwiththefatalneurodegenerative diseaseamyotrophiclateralsclerosis(ALS)arepoorlyunderstoodandearliersmallerstudieshaveshownconflictingresults. Themetabolomic methodology is suitablefor screeninglargecohorts of samples. Globalmetabolomics canbe usedfor detectingchangesofmetaboliteconcentrationsinsamplesoffluidssuchasCSF. Methodology:Usinggaschromatographycoupledtomassspectrometry(GC/TOFMS)andmultivariatestatisticalmodeling, wesimultaneouslystudiedthemetabolomesignatureof,120smallmetabolitesintheCSFofpatientswithALS,stratified accordingtohereditarydispositionandclinicalsubtypesofALSinrelationtocontrols. PrincipalFindings:Thestudyisthefirsttoreportdatavalidatedovertwosub-setsofALSvs.controlpatientsforalargeset 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 heterogeneousthanSALS.Themetabolomeofthecerebrospinalfluidof17ALSpatientswithaSOD1genemutationwas found to form a separate homogeneous group. Analysis of metabolites revealed that glutamate and glutamine were reduced,inparticularinpatientswithafamilialpredisposition.Therear

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