Alzheimer

541 Pages·2007·14.84 MB·English

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
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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