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Alzheimer: 100 years and beyond PDF

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researchandperspectivesinalzheimer’sdisease FondationIpsen Editor YvesChristen,FondationIpsen,Paris(France) EditorialBoard YvesAgid,HôpitalPitiéSalpêtrière,Paris(France) AlbertAguayo,McGillUniversity,Montreal(Canada) BrianH.Anderton,InstituteofPsychiatry,London(GB) RaymondT.Bartus,Alkermes,Cambridge(USA) AndersBjörklund,UniversityofLund(Sweden) FloydBloom,ScrippsClinicandResearchFoundation,LaJolla(USA) FrançoisBoller,InsermU324,Paris(France) CarlCotman,UniversityofCalifornia,Irvine(USA) PeterDavies,AlbertEinsteinCollegeofMedicine,NewYork(USA) AndreDelacourte,InsermU422,Lille(France) StevenFerris,NewYorkUniversityMedicalCenter,NewYork(USA) Jean-FrançoisFoncin,HôpitalPitiéSalpêtrière,Paris(France) FrançoiseForette,HôpitalBroca,Paris(France) FredGage,SalkInstitute,LaJolla(USA) DmitryGoldgaber,StateUniversityofNewYorkStoneBrook(USA) JohnHardy,NationalInstituteofHealth,Bethesda(USA) Jean-JacquesHauw,HôpitalPitiéSalpêtrière,Paris(France) ClaudeKordon,InsermU159,Paris(France) KennethS.Kosik,HarvardMedicalSchool,CenterforNeurological DiseasesandBrighamandWomen’sHospital,Boston(USA) JacquesMallet,HôpitalPitiéSalpêtrière,Paris(France) ColinL.Masters,UniversityofMelbourne,Parkville(Australia) StanleyI.Rapoport,NationalInstituteonAging,Bethesda(USA) BarryReisberg,NewYorkUniversityMedicalCenter,NewYork(USA) AllenRoses,DukeUniversityMedicalCenter,Durham(USA) DennisJ.Selkoe,HarvardMedicalSchool,CenterofNeurological DiseasesandBrighamandWomen’sHospital,Boston(USA) MichaelL.Shelanski,ColumbiaUniversity,NewYork(USA) Pierre-MarieSinet,HôpitalNecker,Paris(France) PeterSt.George-Hyslop,UniversityofToronto,Toronto(Canada) RobertTerry,UniversityofCalifornia,LaJolla(USA) EdouardZarifian,CentreHospitalierUniversitaire,Caen(France) M. Jucker K. Beyreuther C. Haass R.M. Nitsch Y. Christen (Eds.) Alzheimer: 100 Years and Beyond With143Figures 123 MathiasJucker KonradBeyreuther DepartmentofCellularNeurology CentreforMolecularBiology HertieInstituteforClinicalBrainResearch TheUniversityofHeidelberg UniversityofTübingen NeuenheimerFeld282 72076Tübingen 6900Heidelberg Germany Germany e-mail:[email protected] e-mail: [email protected] ChristianHaass RogerM.Nitsch Adolf-Butenandt-Institute DivisionofPsychiatryResearch DepartmentofBiochemistry UniversityofZurich LaboratoryforAlzheimer’s 8008Zurich andParkinson’sDiseaseResearch Switzerland Ludwig-Maximilians-University e-mail:[email protected] 80336Munich Germany YvesChristen e-mail:[email protected] FoundationIPSEN PourlaRechercheThérapeutique 24,rueErlanger 75781ParisCedex16 France e-mail:[email protected] CoverillustrationbyIngramPinn ISSN 0945-6066 ISBN-10 3-540-37651-8 SpringerBerlinHeidelbergNewYork ISBN-13 978-3-540-37651-4 SpringerBerlinHeidelbergNewYork Thisworkissubjecttocopyright.Allrightsarereserved,whetherthewholeorpartofthematerialisconcerned, specificallytherightsoftranslation,reprinting,reuseofillustrations,recitation,broadcasting,reproduction onmicrofilmorinanyotherway,andstorageindatabanks.Duplicationofthispublicationorpartsthereof ispermittedonlyundertheprovisionsoftheGermanCopyrightLawofSeptember9,1965,initscurrent version,andpermissionsforusemustalwaysbeobtainedfromSpringer.Violationsareliableforprosecution undertheGermanCopyrightLaw. SpringerisapartofSpringerScience+BusinessMedia springer.com ©Springer-VerlagBerlinHeidelberg2006 Theuseofgeneraldescriptivenames,registerednames,trademarks,etc.inthispublicationdoesnotimply, evenintheabsenceofaspecificstatement,thatsuchnamesareexemptfromtherelevantprotectivelawsand regulationsandthereforefreeforgeneraluse. Productliability:Thepublisherscannotguaranteetheaccuracyofanyinformationaboutdosageandappli- cationcontainedinthisbook.Ineveryindividualcasetheusermustchecksuchinformationbyconsulting therelevantliterature. Editor:SimonRallison Deskeditor:AnneClaus Coverdesign:WMXDesign,Heidelberg,Germany Typesettingandproduction:LE-TEXJelonek,Schmidt&VöcklerGbR,Leipzig,Germany Printedonacid-freepaper 27/3100/YL 543210 SPIN11808305 Acknowledgements TheeditorswishtothankSimoneEberle,AstriddeGerardandthelocalcommittee fortheorganisationofthemeetinginTübingenandMary–LynnGagefortheediting ofthebook OnehundredyearsofAlzheimerresearch Fewmedicalorscientificaddresseshavesounmistakeablymadehistoryasthepresenta- tiondeliveredbyAloisAlzheimeronNovember4,1906inTübingen.Theone-hundred year anniversary of that event has been marked on several occasions in 2006, most notablyattheverysiteoftheoriginallecture,namelytheInstituteofPsychiatryofthe UniversityofTübingeninGermanyonNovember2–5,2006. Thecelebratoryevent,“Alzheimer100YearsandBeyond”organizedontheiniti- ationoftheAlzheimercommunityinGermanyandworldwide,incollaborationwith theFondationIpsen,wasthehighlightoftheYearofAlzheimer.However,beyondthese fewmonthsoftributes,thecentennialoffersauniqueopportunitytoassessboththe progress achieved and the uncertainties remaining. This volume, a collection com- prised mainly of articles by the invited speakers and also of a few other prominent researchers,ismeanttobearecordofthoseevents. OverthelastcenturyofAlzheimerresearch(1906-2006),remarkableprogresshas beenachievedinmanyareas: – Progresstowardsunderstandingthepathogenesis:Inthisfieldprogresshasbeenvery muchdependentondevelopmentsintechnologyandotherspecialityareas.Thiswas truefromtheverystart:AloisAlzheimer’sresearchwouldnothavebeenpossible without then-nascent microscopic staining techniques. It has proven true again overthelastfewdecades,withmolecularandcellularbiology,genetics,andbrain imagingallmakingcontributionswhilebenefitingfromrelatedfields.Forinstance, thediscoveryoftheroleofapolipoproteinEenabledAlzheimerscientiststoapply research findings from the cardiovascular field. On the other hand, research into the pathogenesis of Alzheimer’s disease revealed fundamental findings regarding proteinaggregation,orregulatedintramembraneproteolysisthathasnotonlybeen appliedtootherneurodegenerativediseasesbutalsopavedtheroadtounderstanding completelyunexpectedsignallingpathways. – Recognitionofthediseaseandclinicaltreatment.Althoughnocurehasbeenfound forAlzheimer’sdiseaseyet,theoutlookispromising.Alzheimer’sdiseasehasceased tobeconsideredasaninescapableconsequenceofageing. – Economicandsocialconsiderations.Withtheagingofoursocietyoverthelast100 years, there has been a continuousincrease in the number of Alzheimer patients andtheburdenforindividualcare-takers,aswellassocialandmedicalinstitutions. Demographyhashelpedtomakethepublicawareandpreparedofthesocialand economicconsequencesofthisdevastatingformofdementia. Yet,noneoftheadvancesmadehaveyetculminatedinafullysatisfactoryoutcome. Thepathogenicmechanismsofthediseaseremaininadequatelyunderstoodandareat VIII OnehundredyearsofAlzheimerresearch thecentreofseriouscontroversy,suchasdeterminingwhethertheobservedlesionsin postmortembrainsofpatientswithAlzheimer’sdiseasearethecauseoraconsequence ofthedisease;innocountryhavethepublicauthoritiesprovidedfullyforpatients; andtreatmentoptionsremainlargely insufficient,despitehopefrom varioussymp- tomatictreatmentsandongoingpromisingclinicalstudiestargetingthepathological mechanisms. Despitetheseshortcomings,thelastonehundredyearshavebeenfullandactive ones. The aim of the meeting held in November 2006 in Tübingen, like that of this volume,isnottolayoutthefinallegacyofascientificcorpusthatis,tothecontrary, constantly-developing,nortocrownthecontributionsofaspecificresearcher,atthe expenseofhiscolleaguesorcompetitors.Instead,itistohonortheworkaccomplished andprovidematerialforthehistoryofscience.Weaskedtheinvitedauthorstopresent theirpioneeringresearchexplainingtheconditionsunderwhichtheywereconducted from their viewpoint, and thus intentionally leaving room for a certain degree of subjectivity.Theirtestimonialscontainunavoidablysomecontradictions,inparticular regardingtheirpartincertainessentialdiscoveries.Theeditorsofthisbookdidnot, atanytime,wishtotakesidesinthepossibleownershipsquabbles,butonlytoprovide readerswithinformationfromtheveryindividualswhohavemadeAlzheimerresearch whatitis,overthepastfewdecades.Theonlyeditingchangesrelatedtoformalone-no articlewaschangedinsubstance,nonewerecensuredandnonewererejected.Some authorsinvitedtopresenttheirresearchatthemeetinginTübingenwereunabletohand intheircontributionsintime,howevercontributedsignificantlytothemeeting,such asMoniqueBreteler,NickFox,MichaelHutton,StevenPaul,GerardD.Schellenberg, SangramS.Sisodia,BengtWinblad,BruceYankner. Lastly, several of the pioneers passed away too early to be able to attend the Tübingen meeting and contribute to this work: George Glenner, Henry Wisniewski, Tsunao Saitoh, Eva Braak, Jean-Louis Signoret, Yvon Lamour, Nelson Butler, Luigi Amaducci,andothers.Wededicatethisvolumetothem. MathiasJucker KonradBeyreuther ChristianHaass RogerNitsch YvesChristen Some“players”oftheADstory(1987–2006) OnehundredyearsofAlzheimerresearch XI 01Paris,1988,StanleyRapoport,CharlesEpstein 02Paris,1988,CarletonGajduzek,HenryWisniewski 03Paris,1987,DennisSelkoe 04Angers,1987,frontrow:AnnickPouplard-Bartheleix,ToshiharuIshii,MrsIshii,TaiheiMiyakawa–backrow: PhilippeBrachet,ColinMasters,KonradBeyreuther,HughFudenberg,HenryWisniewski,MrsGlenner,George Glenner,JacquelineMervaillie,MrsMiyakawa,DennisSelkoe,JeanEmile,PietEikelenboom,JeanLapresle,Yves Christen,AndréDelacourte 05Angers,1987,ToshiharuIshii,YvesChristen,GeorgeGlenner 06Paris,1988,CarletonGajduzek,YvesChristen,FrançoiseForette XII OnehundredyearsofAlzheimerresearch 07Montpellier,1988,AllenRoses,AnnieSaunders 08Paris,1989,MarshalFolstein,StanleyRapoport 09Toulouse,1989,TsunaoSaitoh,RudolphTanzi 10Toulouse,1989,Jean-JaquesHauw 11Paris,1988and2006(CharlesdeGaulleairport),ChristineVanBroeckhoven 12Toulouse,1989,JohnBlass,PeterDavies 13Toulouse,1989,AndréRascol,Jean-LouisSignoret 14Toulouse,1989,RudolphTanzi,YvesAgid 15Toulouse,1989,AndréDelacourte,HenryWisniewski,KrystinaWisniewski,TsunaoSaitoh,UshiBeyreuther, KonradBeyreuther,AndrewHaynes,JohnAtack,JayPettergrew,FrançoisBoller,JacquelineMervaillie,Yves Christen,KennethKosik

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Few medical or scientific addresses have so unmistakeably made history as the presentation delivered by Alois Alzheimer on November 4, 1906 in Tübingen. The celebratory event, ""Alzheimer 100 Years and Beyond"" organized on the initiation of the Alzheimer community in Germany and worldwide, in co
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