Estrogen- AD - Mt?Brain estrogen deficiency accelerates Aβ plaqueformationinanAlzheimer'sdiseaseanimalmodelXuYue*,Melissa Lu*,Techie Lancaster*,Phillip Cao*,Shin-lchiro Hondat,Matthias Staufenbielt,Nobuhiro HaradatZhenyu Zhongs,Yong Shens,and Rena Li19198-192031PNAs1December27,2005/vol.102/no.52Table 1.Clinical and biochemical characteristics of the study subjectsBrainestradiol,pg/mgofproteinSerumestradiol,pg/mABEducation,MMSETotalFreeTotalFreePatientNo.Age, ydensityFree indexFree indexyscoreNon-AD10.71084 ± 2.027.41.63150.6±14.38.3 ± 7.13.1 ± 2.544.4 ± 10.328.3 ± 4.813.5 ± 6.210AD10.65.713.2584 ± 1.8960.0±13.46.8±1.611.9 ± 1.87.0 ± 3.82.1± 1.411.5 ±5.4NSNSNSNSNSPvalueNS0.0010.0020.030.0020.02MMSE,Mini-MentalStateExamination;NS,notsignificant
Estrogen– AD – Mt?
A40brainserum(o302010-3612Age (months)BSHAMAPPDOVXAPPDAPPIAr+/140120(%)1008060*￥40*大20光大大0SERUMBRAINFig.1.Estrogenlevelsinmice.(A)Total17β-estradiolwasdetectedbyRlAintheserumandbrainfromAPP23/Ar+/-(n=10)andAPP23(n=10)miceatvariousages.(B)TwelveAPP23micewereOVXorsham-operatedat3monthsofage.By6monthsofage,levelsoftotal17p-estradiolweremeasured,inbothserumandbrainfromAPP23/Ar+/-(n=10),OVXAPP(n=7),SHAMAPP23(n=5),ornalveAPP23(n=10)mice.*,P<0.01;**,P<0.001(comparedwithnalveAPP23controlmice)
APPOVXAPPAPP/Ar+/-BAC6MED一12MDFig.2.Theplaque formations inthebrainsof6-and12-month-oldmice.FourteenAPP23micewereOVXat3monthsofage.Atageof6or12monthsanimalswerekilledandbrainswerepreparedforimmunohistochemistry.Shownisanti-Aβ(1-17(6E10cloneantibody)immunostainingofsagittalbrainsectionsfromAPP23(n=10:AandD).OVXAPP23(n=7:BandE),andAPP23/Ar+/-(n=10;CandF)miceaged6(A-C)and12(D-F)months
TABLE1IONGOINGCLINICALTRIALSFORTREATINGALZHEIMER'SDISEASEPhaseProposedmechanismofactionApproachordrugB-SecretaseinhibitionDecreasesformationofAβfromamyloidprecursorprotein/IlIy-Secretase inhibitionDecreasesformationofAβfromamyloidprecursorproteinIlActiveimmunizationwithAβGenerates anti-Aβantibodiesthatinteract withAβand remove itpeptidesfromthebrainbyuncertaindownstreammechanismsIIPassiveimmunizationwithTheantibodies interactwithAβand remove itfromthebrainbyanti-Aβantibodiesuncertaindownstream.mechanismsI川IIntravenouspooledMayenhanceclearanceofAβandotherharmfulproteinsfromtheimmunoglobulinsbrain;maydecreaseharmfulinflammatoryprocesses1Scyllo-inositolDecreasesformationandstabilityofpathogenicAβassemblies川LatrepirdinePreventsmitochondrial dysfunction1lInhibitionofreceptorforBlocksstimulationofthecell-surfacereceptorRAGE,whichbindsadvancedglycationAβ,decreasingAβlevelsinthebrainandpreventingAβfromendproducts(RAGE)activatingpathogenicpathwaysIStimulationofinsulin signallingPreventshyperglycaemiamayovercomeinsulinresistanceinthebrain11Selective oestrogen-receptorPromotesneuroprotective effectsofoestrogenwithoutelicitingmodulatoritsharmfuleffects1NeurotrophicandStimulateneurotrophicandantioxidantpathwaysorpathwaysneuroprotectiveagentsthatprotectagainstexcitotoxicityTheaboveselectionfocusesonpotentiallydisease-modifyingstrateglesandisbasedonareviewofwebsites,oralreportsatscientificmeetings,and discussionswithPaulAisen (UniversityofCalifomla,San Diego)and LaurleRyan (National InstituteonAging).Phasellandphaselltrialsassessthesafetyandefficacyofnewtreatments:phaselll trlals involvemanymoresubjects,afeconductedinmultiplecentres,andarerequiredfordrugapprovalbyregulatoryagencles
Prevention program for AD and age-relateddecline in motor function was established中华人民共和国闵家知识产权制中华人民共和国国家知识产友局Atttnh100088100088ERSHes-Ler(sDS0E2E1I54OR2E中电：0专科信受理通如书专科申请受理通相书39：1BnHDHR车用2JRA：MRTASMNEAEbNTSB电：品工作司k-nEWEERARMEReeFEEOTE/NTHOERUE3K8ANte工TESaeeeSRE+ntrtgeTW防治老年痴呆病的线粒体改善衰老相关运动功能衰退的营养素应用线粒体营养素应用Application of MitochondrialApplication of mitochondrialNutrientsinPreventionandnutrients to ameliorateaging30TreatmentofAlzheimer'sDiseaserelatedmotorfunctiondecline
Prevention program for AD and age-related decline in motor function was established 防治老年痴呆病的线粒体 营养素应用 Application of Mitochondrial Nutrients in Prevention and Treatment of Alzheimer's Disease 改善衰老相关运动功能衰退的 线粒体营养素应用 Application of mitochondrial nutrients to ameliorate agingrelated motor function decline 30