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