Peptide Fingerprinting of Alzheimers Disease in Cerebrospinal Fluid Identification and Prospective Evaluation of New Synaptic Biomarkers 英文参考文献.docVIP

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Peptide Fingerprinting of Alzheimers Disease in Cerebrospinal Fluid Identification and Prospective Evaluation of New Synaptic Biomarkers 英文参考文献.doc

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Peptide Fingerprinting of Alzheimers Disease in Cerebrospinal Fluid Identification and Prospective Evaluation of New Synaptic Biomarkers 英文参考文献

PeptideFingerprintingofAlzheimer’sDiseasein CerebrospinalFluid:IdentificationandProspective EvaluationofNewSynapticBiomarkers HolgerJahn1*.,StefanWittke2,3.,PetraZu¨rbig2,ThomasJ.Raedler1,4,So¨nkeArlt1,MarkusKellmann5, WilliamMullen6,MartinEichenlaub1,HaraldMischak2,6,KlausWiedemann1 1DepartmentofPsychiatry,UniversityHospitalHamburg-Eppendorf,Hamburg,Germany,2MosaiquesDiagnosticsGmbH,Hannover,Germany,3UniversityofApplied Sciences, Bremerhaven, Germany, 4Department of Psychiatry, Foothills Hospital, University of Calgary, Calgary, Canada, 5Thermo Fisher Scientific GmbH, Bremen, Germany,6BHFGlasgowCardiovascularResearchCentre,UniversityofGlasgow,Glasgow,UnitedKingdom Abstract Background:Today,dementiasarediagnosedlateinthecourseofdisease.Futuretreatmentshavetostartearlierinthe diseaseprocesstoavoiddisabilityrequiringnewdiagnostictools.Theobjectiveofthisstudyistodevelopanewmethodfor thedifferentialdiagnosisandidentificationofnewbiomarkersofAlzheimer’sdisease(AD)usingcapillary-electrophoresis coupledtomass-spectrometry(CE-MS)andtoassessthepotentialofearlydiagnosisofAD. MethodsandFindings:Cerebrospinalfluid(CSF)of159out-patientsofamemory-clinicataUniversityHospitalsuffering fromneurodegenerativedisordersand17cognitively-healthycontrolswasusedtocreatedifferentialpeptidepatternfor dementiasandprospectiveblinded-comparisonofsensitivityandspecificityforADdiagnosisagainsttheCriterionstandard in a naturalistic prospective sample of patients. Sensitivity and specificity of the new method compared to standard diagnosticproceduresandidentificationofnewputativebiomarkersforADwasthemainoutcomemeasure.CE-MSwas usedtoreliablydetect1104low-molecular-weightpeptidesinCSF.Training-setsofpatientswithclinicallysecuredsporadic Alzheimer’s disease, frontotemporal dementia, and cognitively healthy controls allowed establishing discriminative biomarkerpatternfordiagnosisofAD.Thispatternwasalreadydetectableinpatientswithmildcognitiveimpairment(MCI). TheAD-patternwastestedinaprospectivesampleo