Neuropathology and Genetics of Dementia

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For more than 35 years the Swiss Society of Neuropathology has organiseditstraditionalInternationalWinterMeeting.Themainaimofthis venue is to bring together neuropathologists and clinicians as well as neuroscientistsinterestedindiseasemechanisms.TheXVIIIthInternational WinterMeeting washeld inMarch 2000 in St. Moritz, Switzerland. The topicofthe2000Meetingwas NeuropathologyandGeneticsofDementia . Aprogrammeofinvitedplenarylecturesofhigheducationalvalueaswellas platform andposterpresentations given by manyparticipantscoveredthe broadspectrumofdementingdisorders.Encouragedbythehighstandardof the meeting, and probably also influenced by the advent of a new Millenniumwedecided,togetherwithKluwerAcademiclPlenumPublishers, topublishtheProceedingsofthe2000Meetinginthepresentbook. The increaseofthe agedpopulation challenges social and health care systemsinindustrializedsocieties.Maintenanceofhealthandautonomyinto oldage isakeyfactor,andtheautonomyandindependenceofoldpersons crucially depend on mental health. However, neurodegenerative disorders accompanied bydementiaaffect 5-10%ofindividualsoverthe ageof65, and for the age group between 65 and 95 the prevalence of cognitive dysfunction doubles every 5 years. With this challenge in mind, Rossor discusses the clinical syndrome of dementia which encompasses an enormousvarietyofunderlyingdisorders. Over the last few years it has become apparent that many neurodegenerative disorders are characterised by protein misfolding and aberrant polymerization and may therefore be viewed as aggregation proteopathies . Among them a substantial subsetofdementing disorders, either with or without motor dysfunction, are characterised by abundant v VI Preface neuronaland/orglialaccumulationofhyperphosphorylatedtauprotein.The molecular parametersofthese tauopathies are reviewed by Delacourte. Therecentdiscoverythatmutationsofthetaugenearecausativeforfamilial formsoffrontotemporaldementiaandParkinsonism(FTDP-17)broughtthe taupathway and the tauopathies tothecentrestage.Thisextraordinary breakthroughwillbecoveredbySpillantiniandGoedert.Thereisincreasing evidence that argyrophilic grain disease is much more frequent in older patients than previously thought. Tolnay et al. are reviewing recent contributionstothepathologyofthislate-onsetdementingdisorderinwhich ofamyloidbetadeposits,isalmost taupathology,inthealmosttotalabsence exclusivelyrestricted to the limbic lobe and the amygdala. Schultzet al. report an intriguing age-related progression of neuronal and glial tau pathologyinbaboonsthusrenderingthe baboonapotentialprimatemodel forage-relatedhuman tauopathies . Gotzetal. introducetransgenicmice expressingmutated human tau as valuable animal models for reproducing formationofneuro-andglialfibrillarylesions.