Microglial Activation Correlates with Disease Progression and Upper Motor Neuron Clinical Symptoms in Amyotrophic Lateral Sclerosis 英文参考文献.docVIP

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Microglial Activation Correlates with Disease Progression and Upper Motor Neuron Clinical Symptoms in Amyotrophic Lateral Sclerosis 英文参考文献.doc

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Microglial Activation Correlates with Disease Progression and Upper Motor Neuron Clinical Symptoms in Amyotrophic Lateral Sclerosis 英文参考文献

MicroglialActivationCorrelateswithDiseaseProgression andUpperMotorNeuronClinicalSymptomsin AmyotrophicLateralSclerosis JohannesBrettschneider1,4*,JonB.Toledo1,2,ViviannaM.VanDeerlin2,LaurenElman3,LeoMcCluskey3, VirginiaM.-Y.Lee1,2,JohnQ.Trojanowski1,2 1Center for Neurodegenerative Disease Research (CNDR), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 2DepartmentofPathologyandLaboratoryMedicine,UniversityofPennsylvaniaSchoolofMedicine,Philadelphia,Pennsylvania,UnitedStatesofAmerica,3Department ofNeurology,UniversityofPennsylvaniaSchoolofMedicine,Philadelphia,Pennsylvania,UnitedStatesofAmerica,4DepartmentofNeurology,UniversityofUlm,Ulm, Germany Abstract Background/Aims: We evaluated clinicopathological correlates of upper motor neuron (UMN) damage in amyotrophic lateral sclerosis (ALS), and analyzed if the presence of the C9ORF72 repeat expansion was associated with alterations in microglialinflammatoryactivity. Methods:MicroglialpathologywasassessedbyIHCwith2differentantibodies(CD68,Iba1),myelinlossbyKluver-Barrera stainingandmyelinbasicprotein(MBP)IHC,andaxonallossbyneurofilamentprotein(TA51)IHC,performedon59autopsy casesofALSincluding9caseswithC9ORF72repeatexpansion. Results:MicroglialpathologyasdepictedbyCD68andIba1wassignificantlymoreextensiveinthecorticospinaltract(CST) ofALScaseswitharapidprogressionofdisease.CaseswithC9ORF72repeatexpansionshowedmoreextensivemicroglial pathology in the medulla and motor cortex which persisted after adjusting for disease duration in a logistic regression model.HigherscoresontheclinicalUMNscalecorrelatedwithincreasingmicroglialpathologyinthecervicalCST.TDP-43 pathologywasmoreextensiveinthemotorcortexofcaseswithrapidprogressionofdisease. Conclusions:ThisstudydemonstratesthatmicroglialpathologyintheCSTofALScorrelateswithdiseaseprogressionandis linkedtoseverityofUMNdeficits. Citation:BrettschneiderJ,ToledoJB,VanDeerlinVM,ElmanL,McCluskeyL,etal.(2012)MicroglialActivationCorrela