Soluble Beta-Amyloid Precursor Protein Is Related to Disease Progression in Amyotrophic Lateral Sclerosis 英文参考文献.docVIP

SolubleBeta-AmyloidPrecursorProteinIsRelatedto DiseaseProgressioninAmyotrophicLateralSclerosis PetraSteinacker1,LubinFang1,JensKuhle2,AxelPetzold3,HayrettinTumani1,AlbertC.Ludolph1, MarkusOtto1,JohannesBrettschneider1* 1DepartmentofNeurology,UniversityofUlm,Ulm,Germany,2DepartmentofNeurology,UniversityofBasel,Basel,Switzerland,3DepartmentofNeuroimmunology, UCLInstituteofNeurology/NationalHospitalforNeurologyandNeurosurgery,QueenSquare,London,UnitedKingdom Abstract Background: Biomarkers of disease progression in amyotrophic lateral sclerosis (ALS) could support the identification of beneficialdrugsinclinicaltrials.Weaimedtotestwhethersolublefragmentsofbeta-amyloidprecursorprotein(sAPPaand sAPP?)correlatedwithclinicalsubtypesofALSandwereofprognosticvalue. Methodology/PrincipalFindings:Inacross-sectionalstudyincludingpatientswithALS(N=68)withclinicalfollow-updata over6months,Parkinson’sdisease(PD,N=20),andage-matchedcontrols(N=40),cerebrospinalfluid(CSF)levelsofsAPPa a, sAPP? and neurofilaments (NfHSMI35) were measured by multiplex assay, Progranulin by ELISA. CSF sAPPa and sAPP? levelswerelowerinALSwitharapidly-progressivediseasecourse(p=0.03,andp=0.02)andwithlongerdiseaseduration (p=0.01 and p=0.01, respectively). CSF NfHSMI35 was elevated in ALS compared to PD and controls, with highest concentrationsfoundinpatientswithrapiddiseaseprogression(p,0.01).HighCSFNfHSMI3 waslinkedtolowCSFsAPPa andsAPP?(p=0.001,andp=0.007,respectively).TheratiosCSFNfHSMI35/CSFsAPPa,-?wereelevatedinpatientswithfast progressionofdisease(p=0.002each).CSFProgranulindecreasedwithongoingdisease(p=0.04). Conclusions: This study provides new CSF candidate markers associated with progression of disease in ALS. The data suggestthatadeficiencyofcellularneuroprotectivemechanisms(decreaseofsAPP)islinkedtoprogressiveneuro-axonal damage(increaseofNfHSMI35)andtoprogressionofdisease. Citation:SteinackerP,FangL,KuhleJ,PetzoldA,TumaniH,etal.(2011)SolubleBeta-AmyloidPrecursorProteinIsRelatedtoDisease