Neuropathology and Genetics of Dementia PDF
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NEUROPATHOLOGY AND GENETICS OF DEMENTIA ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY EditorialBoard: NATHAN BACK,State UniversityofNew YorkatBuffalo IRUN R. COHEN.The Weizmann Institute ofScience DAVID KRITCHEVSKY. WistarInstitute ABELLAJTHA.N. S. Kline Institutefor PsychiatricResearch RODOLFOPAOLETTI, UniversityofMilan Recent Volumes in this Series Volume 477 CELLULAR PEPTIDASES IN IMMUNE FUNCTIONS AND DISEASES 2 Edited by Jiirgen Langnerand Siegfried Ansorge Volume 478 SHORTAND LONG TERM EFFECTS OF BREASTFEEDINGONCHILD HEALTH Edited by Berthold Koletzko, Olle Hemell, and Kim FleischerMichaelsen Volume 479 THE BIOLOGY AND PATHOLOGY OF INNATEIMMUNITY MECHANISMS Edited by Yona Keisari and Itzhak Ofek Volume 480 BIOLOGY OFTHEMAMMARYGLAND Edited by Jan A. Mol and Roger A. Clegg Volume 481 ELASTIC FILAMENTS OFTHE CELL Edited by HenkL. Granzierand Gerald H. Pollack Volume 482 CHROMOGRANINS: Functional and Clinical Aspects Edited by Karen B. Helle and Dominique Aunis Volume 483 TAURINE4: Taurine and ExcitableTissues Edited by Laura Della Corte, Ryan J. Huxtable, Giampietro Sgaragli, and Keith F. Tipton Volume 484 PHYLOGENETIC PERSPECTIVES ONTHE VERTEBRATE IMMUNE SYSTEM Edited byGregory Beck, Manickam Sugumaran, and Edwin L. Cooper Volume 485 GENES AND PROTEINS UNDERLYING MICROBIAL URINARY TRACT VIRULENCE: Basic Aspects and Applications Edited by Levente EmOdy,Tibor Pal,Jorg Hacker. and Gabriele Blum-Oehler Volume 486 PURINEAND PYRIMIDINE METABOLISM IN MAN X Edited by EstherZoref-Shani and Oded Sperling Volume 487 NEUROPATHOLOGY AND GENETICS OFDEMENTIA Edited by Markus Tolnay and Alphonse Probst AContinuationOrderPlanisavailableforthisseries.Acontinuationorderwillbringdeliveryofeachnewvolume immediatelyuponpublication.Volumesarebilledonlyuponactualshipment.Forfurtherinformationpleasecontact thepublisher. NEUROPATHOLOGY AND GENETICS OF DEMENTIA Edited by MARKUS TOLNAY and ALPHONSE PROBST University 0/ Basel Basel, Switzerland SPRINGER SCIENCE+BUSINESS MEDIA, LLC Library of Congress Cataloging-in-Publieation Data Neuropathology and genetics of dementialedited by Markus Tolnay and Alphonse Probst. p. em. - (Advanees in experimental medieine and biology; v. 487) ISBN 978-1-4613-5461-1 ISBN 978-1-4615-1249-3 (eBook) DOI 10.1007/978-1-4615-1249-3 I. Dementia-Pathophysiology-Congresses. 2. Dementia-Genetie aspeets-Congresses. 3. Nervous system-Pathophysiology-Congresses. I. Tolnay, Markus, 1962- 11. Probst, Alphonse, 1938- III. Series. RC521 .N47 2001 616.8'3-de21 00-067413 Proceedings of the Swiss Soeiety for Neuropathology XVIIIth International Winter Meeting on Neuropathology and Geneties of Dementia, held Mareh 23-26, 2000, in SI. Moritz, Switzerland ISSN: 0065 2598 ISBN 978-1-4613-5461-1 ©2001 Springer Science+Business Media NewYork Originally published by Kluwer Academic/Plenum Publishers, New York in 2001 Softcover reprint of the hardcover 1s t edition 2001 10987654321 A C.l.P. reeord for this book is available from the Library of Congress All rights reserved No part of this book may be reprodueed, stored in a retrieval system, or transmitted in any form or by any means, eleetronie, meehanieal, photocopying, mierofilming, recording, or otherwise, without written permission from the Publisher Preface For more than 35 years the Swiss Society of Neuropathology has organised its traditional International Winter Meeting. The main aim ofthis venue is to bring together neuropathologists and clinicians as well as neuroscientists interested in disease mechanisms. TheXVIIIth International Winter Meeting was held in March 2000 in St. Moritz, Switzerland. The topic ofthe 2000Meetingwas "NeuropathologyandGenetics ofDementia". Aprogramme ofinvitedplenarylectures ofhigheducational value as well as platform and poster presentations given by many participants covered the broad spectrum ofdementing disorders. Encouraged by the high standard of the meeting, and probably also influenced by the advent of a new Millenniumwedecided, togetherwithKluwerAcademiclPlenumPublishers, to publishthe Proceedings ofthe 2000Meetinginthepresentbook. The increase of the aged population challenges social and health care systems in industrialized societies. Maintenanceofhealthandautonomyinto old age is a key factor, and the autonomy and independence ofold persons crucially depend on mental health. However, neurodegenerative disorders accompanied by dementia affect 5-10% of individuals over the age of 65, 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 enormous variety ofunderlying disorders. 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 subset of dementing disorders, either with or without motor dysfunction, are characterised by abundant v VI Preface neuronal and/or glial accumulation ofhyperphosphorylated tau protein. The molecular parameters of these "tauopathies" are reviewed by Delacourte. The recentdiscovery that mutations ofthe tau genearecausativefor familial forms offrontotemporal dementia and Parkinsonism (FTDP-17) broughtthe "tau pathway" and the "tauopathies" to the centre stage. This extraordinary breakthrough will be covered by Spillantini andGoedert. There isincreasing evidence that argyrophilic grain disease is much more frequent in older patients than previously thought. Tolnay et al. are reviewing recent contributions to the pathology ofthis late-onsetdementing disorderinwhich taupathology, inthe almost total absence ofamyloidbetadeposits, is almost exclusively restricted to the limbic lobe and the amygdala. Schultz et al. report an intriguing age-related progression of neuronal and glial tau pathology in baboons thus rendering the baboon a potential primate model for age-related human "tauopathies". Gotz et al. introduce transgenic mice expressing mutated human tau as valuable animal models for reproducing formation ofneuro- and glial fibrillary lesions. AD is neuropathologically characterised by abundant extracellular amyloid beta deposits (among them the neuritic plaques) and intracellular neurofibrillary tangles. Gandy and Petanceska are reviewing the hitherto proposed mechanisms of amyloid precursor protein (APP) trafficking and metabolism. In additionthey focus ontherecentfindings thatestradiolmight influence the risk or age-at-onset of AD by lowering the speed of the accumulation of amyloid beta protein. The role of type 10 17beta hydroxysteroid dehydrogenase in this process is reviewed by Yang and He. In AD but also in non-demented elderly subjects the amyloid beta protein accumulates in the walls of small cerebral blood vessels (cerebral amyloid angiopathy; CAA). Weller and Preston present evidence for the hypothesis that CAA results from the accumulation ofamyloid peptides in perivascular interstitial fluid drainage pathways and that the impedence of drainage of amyloid beta protein from the brain may contribute to the onset ofAD. The contribution by Herzig et al. on APP transgenic mice which develop abundant CAA is in line with this hypothesis. Lewy bodies and Lewy neurites are hallmark lesions of Parkinson's disease (PD) and Dementia with Lewy bodies (DLB), and the main protein constituent of these lesions is the presynaptic protein alpha-synuclein. Alpha-synuclein is also present in glial cytoplasmic inclusions ofmultiple system atrophy (MSA), and therefore PD, DLB and MSAhave been lumped under the term "alpha-synucleinopathies". Jensen and Gai review therole of alpha-synuclein in neurodegeneration while the contributionby Ince focuses on the relationship between AD, PD and DLB at the clinicopathological level. Recent findings in vivo intransgenic flies and transgenicmice provide novel perspectives to model in animals the pathophysiology ofdiseases with Preface VB alpha-synucleinopathy. These new aspects are covered by the contribution by Barbieri etal. A large number of disease-related cellular fea,tures can be detected by ubiquitin immunohistochemistry. While for some disorders the molecular nature of the ubiquitinated filamentous inclusions is well known, e.g. amyloid beta protein, tau protein, alpha-synuclein and huntingtin, there is a substantial subset ofneurodegenerative disorders for which the nature ofthe pathological protein complexed with ubiquitin still remains unknown. Among others, motor neuron disease, frontotemporal dementia with inclusions of motor neuron disease type and some cases of primary progressive aphasia and semantic dementia belong to this group of "ubiquitindisorders". The involvementofthe ubiquitin systemin diseasesof the nervous system will be covered by Lowe et al. Furthermore, using ubiquitin-immunohistochemistry, Probst et al. describe a novel type of hippocampal ubiquitinpathology inAD and Pick's disease. Polyglutamine expansion diseases such as Huntington's disease, spinobulbar muscular atrophy and spinocerebellar ataxia constitute a subset of "proteopathies" in some of which there are abundant neuronal intranuclear polyglutamine inclusions. The pathological mechanisms underlying these disorders will bereviewedbyDevys etal. Though most of us would associate the term dementia with old age, dementia may also occur in the pediatric age group in a variety of progressive neurological disorders. The contribution by Goebel and Kohlschiitter deals with the presence of dementia in the neuronal ceroid lipofuscinoses. Thereader mightaskwhyinclusion bodymyositis (IBM) isincluded ina book devoted to dementia. However, it has become apparent in the last few years that IBM inclusions encompass a wide range ofproteins involved in neurodegenerative dementing disorders, such as APP, tau, presenilin-l, apolipoprotein E and prion protein. Lampe et al. are focusing on the role of neurodegeneration-associatedproteins inIBM. Last, but not least, the book closes with the contribution by Turner and Schapira who critically review the evidence for the role of mitochondrial dysfunction in a wide range ofneurodegenerative disorders and the ageing brain. Together with the contributors we believe that this bookwill not only be useful to neuropathologists but also to clinicians and basic scientists interested in the broad field ofdementia. Markus Tolnay AlphonseProbst Acknowledgments We thank the authors for their contributions, the publishers, particularly Joanna Lawrence, for their help in the production ofthis book and Thomas Schiirch and Michelle Pfeiffer for their photographic and administrative help. Finally, we are grateful to Kurt Brauchli who guided us safely through all expected,butevenmore important,unexpectedcomputerproblems. MarkusTolnay AlphonseProbst IX Contents CANTHEPHYSICIANPREDICTTHENEUROPATHOLOGIST? MartinN. Rossor 1 THEMOLECULARPARAMETERS OFTAUPATHOLOGY Tau as a killerandawitness AndreDelacourte , ,'" 5 TAUGENE MUTATIONSAND TAUPATHOLOGYIN FRONTOTEMPORALDEMENTIAANDPARKINSONISMLINKEDTO CHROMOSOME 17 MariaG. SpillantiniandMichelGoedert 21 ARGYROPHILIC GRAINDISEASE Afrequent dementingdisorderin agedpatients MarkusTolnay,AndreasU. MonschandAlphonseProbst 39 TAUPATHOLOGYINNEURONSANDGLIALCELLSOFAGED BABOONS ChristianSchultz, Gene B. Hubbard, KellyDelTredici,EvaBraakand HeikoBraak 59 Xl XII Contents HUMANTAUTRANSGENIC MICE Towards an animalmodelfor neuro-andglialfibrillarylesionformation JiirgenG6tz, MarkusTolnay,RobiBarmettler,AlessandraFerrari,KurtBiirki, MichelGoedert, AlphonseProbstandRogerM. Nitsch 71 REGULATIONOFALZHEIMERI3-AMYLOIDPRECURSOR TRAFFICKINGAND METABOLISM SamuelGandyandSuzanaPetanceska 85 ROLE OFTYPE 10 1713-HYDROXYSTEROIDDEHYDROGENASEIN THE PATHOGENESISOFALZHEIMER'SDISEASE Song-YuYang andXue-YingHe 101 THE SPECTRUMOFVASCULARDISEASEINDEMENTIA From ischemia to amyloidangiopathy Roy O. WellerandStephenD. Preston 111 TRANSGENICMOUSEMODELSOFCEREBRALAMYLOID ANGIOPATHY MartinC. Herzig, DavidT. Winkler, LaryC. WalkerandMathiasJucker 123 ALPHA-SYNUCLEIN Axonaltramport, ligandinteractionandneurodegeneration PoulHenningJensenand WeiPingGai 129 DEMENTIAWITHLEWYBODIES PaulIllce 135 MOUSE MODELSOFu-SYNUCLEINOPATHYANDLEWY PATHOLOGY a-synuclein expression in transgenicmice SamuelBarbieri, KatjaHofele,Karl-HeinzWiederhold, AlphonseProbst, ClaudiaMistl, SimoneDanner, SabineKauffmann, BerndSommer,Willibrordus Spooren, MarkusTolnay, GraemeBilbeandHermanvanderPutten 147 UBIQUITIN ANDTHEMOLECULARPATHOLOGYOF NEURODEGENERATIVEDISEASES James Lowe, JohnMayer,MichaelLandonandRobertLayfield 169
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