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Alzheimers()(100043)(Alzheimersdisease,AD)AD,;AD,,81%88%[1],,(SPECT),(PET)CT,-AP,ADAD;,;,(-amyloid,A)Tau,(senileplaques,SP)(NFT)AADAAD:A3943,4104.2KD,(APP),,3APP795APP270Kunitz,,APP,APP(sAPP)APPA,A,AAPP3,,,A[1]AAA,,,,Ca2+,,,,[2],A,;EA,AA,AD[3];A1-40,21030:A1-40,3A1-40,45,A1-40Nitta[4]A2,A,AAButterfieldBeckman[5]A,,AA,PA-1,2AD:APP,211112APPA;A[6][7]114PS-2PS-1ADPS,,PS-1PS-2,,ADPS-1AAPP,PS-2APP[8]Walter[9]AP-1,2APPPS-1,2APP,PS-1,2APP,A,,,,3943,C,C,PSCAPP,A[8];,APP,A,APP,APP;SimonAPP[10],SimonApoEAD:,E(ApoE)-SPApoE299ApoE,,,ApoE(LDL),ApoBApoE(LDL),,ApoE,ApoEA,ApoELDL(LRP)AE3E4LRP,E3AE4,ApoE4AApoE-AE4,E4-A,AAD[11]AD:2132001145,,40%,AD,,(TAC),-(-KGDH)-A,,AD,,,-KGDH;-AP,AD-KGDH[12]AD:():,ADADAD,80AD;,,,()AD,,AD,SPECTPETAD,ADSPECT,;SPECT,AD,1991Goldstein[13]SPECT,1992Pealson[14]SPECT,MRI,SPECTADMRIAD1995Gonza2lez[15]MRIPETAD,AD/,78%Yamaguchi[16]MRI,PETAD,AD,,,,AD1998Tohgi[17]PETAD,,Johnson[18]SPECTAD,(),2000[19]18F-(FDG)PET,,MRI,18F-FDGPETAD;():AD-AP,(APP);,APP28,(1-28),,SAPP,-AP,,APP,A39-44A39-43,-AP-AP,,,-AP(1-28),-AP,,-AP,30119-AP,-AP,AD,;,,ADMRI,SPECTPET,,-APAD;,AD,;AD[1]ReiterRJ.Oxidativedamageinthecentralnervoussysterm:protecoinbymelatonin.ProgNeurobio1999;57:301[2]Behl.Alzheimersdiseaseandoxidativestres:implicationsfornoveltherapeuticapproches.ProgNeurobio1998;56:359[3],2000;23(3):150[4]NittaA,ItohA,HasegawaT.Beta-AmolidproteininducedAlzheimersdiseaseanimalmodel.NeurosciLett1994;170(1):63[5]ButterfieldDA,HensleyK,HarrisME,etal.Beta-amyloidpwptidefreeradicalfragmentsinitiatesynaptosomallipoperoxidationinasequence-speoificfashion:implicationstoAlzheimersdisease.BiochemBiophtsResCommrn1994;200(2):710[6]PauseyRV,KrishnanKR.AnewMRIrationethiedforin-vivoestima2tionofsignalhypointensityinagingandAlzheimers.ProgNeuropry-chopharmacolBiopsychiatry1997;21:1257[7]2000;5:150[8]WeidemannA,PalignK,DurrwangK,etal.Formatingofstablecom2plexesbetweentwoAlzheimersdiseasegeneproduce:presenilin-2andbeta-amyloidprecussorprotein.NetMed1997;3(3):328[9]WalterJ,CapellA,GrunbergJ,etal.YheAlzheimersdiseaseassoci2atedpresenilinsaredifferentiallyphosphorylatedproteinslocatedpredominant2lywiththeendoplasmicveticulum.MolMed1996;2(6):673[10]SimonsM,IlonenE,TienariPj,etal.Intracellrarroutingofhumanamyloidproteinprecursor:axonaldeliveryfollowedbytransporttotheden2drite.JNeurosicRes1995;41:121[11]MetzgerRE,LaduMJ,PanJB,etal.Neuronsofthehumanfrontalcor2texdisplayapolipoproteinEimmunoreactivity:implicationsforAlzheimersdisease.JNeuropatholExpNeurol1996;55(30):372[12]LandinK,TueekS,RicuyR,etal.Lowcloodpressandbloodglucose3132001145levelsinAlzheimersdisease,Evidenceforahypometabolicdisorder?JIn2ternMed1993;233:357[13]GoldsteinS,ReivichV.Cerebralbloodflowandmetabolisminaginganddementia.Neuropharmaclol1991;14(suppl):34[14]PelsonGd,HarisGj,PoersRE,etal.Quantitativechangesinmesialtemporalvolrmeregionak:bralbloodflowandcognitioninAlzheimersdis2ease.ArchGenPsychiatry1992;49:402[15]GonzalezRG,AlanJF,AlexanderRG,etal.FunctionalMRinthee2valuationofdementia:CorrelationofabnomaldynamiccerebaralincerebralmetabolismonpositronemissiontomographywithfludeoxgoucosiF18.AJNR1995;16:1763[16]YamaguchiSMeguroK,ItohM,etal.DecreasedcorticalglucosemetabolismcorrelateswithhippocampalatrophyinAlzheimersdiseaseasshownbyMRIandPET.JNeurolNeurosurgPsychiatry1997;62:596[17]TohgiH,YonezawaH,TakahashiS,etal.CerebralbloodflowandoxygenmetabolisminseniledementiaofAlzheimerstypeandvascularde2mentiswithdeepwhitematterchanges.Neuroradiology1998;40:131(200173)HP(214041)55814C-(HP)86%;70%;49%;4714%;38%;14C-HP:2000120011,,558,14C-326,1681,4718;232,1679,4912:,1Ci/14-,20ml,320ml,,,,,YH0114C-HP,11HP()HP(%)2068(47)1872(5216)828158(7017)57(7013)4565(54)4467(50)251612(4810)8(5010)3162(4912)2569(4612)25389(3610)15(3914)1662(4516)3071(4712)254012(4918)18(4510)2079(50165)1681(4312)7515165(8617)30(8610)HP,(P0.05)HP,HP,HP(P0.05),14C-BUTHP,30,,HP86%,80%100%[1]HP70%,HPHP,,,,HP,,HP[2],HP,HPHP,,;HP,HP,HP,HP,[3],--E2,,(DGM),(DV)DV,,,HPHP(DV)4132001145