Pathobiology of Alzheimer's Disease (Neuroscience Perspectives)

256 Pages·1995·0.32 MB·English

by  Alison M. Goate

Pathob iology
of
Alz he i me r’s Disease
NEUROSCIENCE PERSPECTIVES
Series Editor
Peter Jenner
Pharmacology Group
Biomedical Sciences Division
King's College London
Manresa Road
London SW3 6LX
Editorial Advisory Board
Floyd E. Bloom The Scripps Research Institute, LaJolla, California, USA
David A. Brown University College London, London, UK
Arvld Carlsson University of Goteborg, Sweden
Ermlnio Costa Nathan Kline Institute for Psychiatric Research, Orangeburg,
New York, USA
KjeU Fuxe Karolinska Institute, Stockholm, Sweden
Gian L. Gessa University of Cagliari, Italy
Paul Greengard The Rockefeller Univers@, New York, USA
Herbert Y. Meltzer Case Western Reserve University, Cleveland, Ohio, USA
Salvador Moncada WellcomeR esearch Laboratories, Beckenham, Kent, UK
Solomon H. 8nyder Johns Hopkins Universi~, Baltimore, USA
Tides in this series
Roger Horton and Cornelius Katona (eds), Biological Aspects of Affective Disorders
Trevor Stone (ed), Adenosine in the Nervous System
Judith Pratt (ed), The Biological Bases of Drug Tolerance and Dependence
Michel Hamon (ed), Central and Peripheral 5-HT~ Receptors
John Waddington (ed), D, :D2 Dopamine Receptor Interactions
Thomas Barnes (ed), Antipsychotic Drugs and Their Side-Effects
Eva Giesen-Crouse (ed), Peripheral Benzodiazepine Receptors
David Nicholson (ed), Anti-Dementia Agents
Alan Harvey (ed), Natural and Synthetic Neurotoxins
John Wood (ed), Capsaicin in the Study of Pain
Yossefltzhak (ed), Sigma Receptors
Pathobiology
of
Alzheimer's Disease
edited by
Alison M. Goate and Frank Ashall
Department of Psychiatry,
St Louis University School of
Medicine, St Louis, USA
ACADEMIC PRESS
Harcourt Brace & Company, Publishers
London San Diego New York
Boston Sydney Tokyo Toronto
ACADEMIC PRESS LIMITED
24/28 Oval Road,
London NW1 7DX
United States Edition published by
ACADEMIC PRESS INC.
San Diego, CA 92101
This book is printed on acid free paper
Copyright (cid:14)9 1995 by Academic Press Limited
All Rights Reserved
No part of this book may be reproduced in any form by photostat, microfilm, or any other means,
without written permission from the publishers
A catalogue record for this book
is available from the British Library
ISBN 0-12-286965-6
Typeset by Servis Filmsetting Ltd, Manchester, UK
Printed and bound in Great Britain
by TJ Press, Padstow, Cornwall.
Contents
Contributors ix
Series Preface xi
...
Preface Xlll
1 Plaques and tangles in Alzhekner’s disease: a historical
introduction 1
R Ashall
1.1 The Alzheimer century 1
1.2 Early history of dementia and Alzheimer’s disease 2
1.3 Alois Alzheimer and his disease 4
1.4 Further progress with plaques and tangles 5
References 6
2 Structure, biochemistry and molecular pathogenesis of paired
helical filaments in Alzheimer’s disease 9
C. M. Wischik, R. Lai, C. R. Harrington, E. Mukaetova-Ladin-ska,J . Xuereb,
R. Mena, l? Edwards and M. Roth
2.1 The anatomy of neurofibrillary degeneration 9
2.2 The ultrastructure of neurofibrillary tangles 12
2.3 Molecular analysis of the PHF core 13
2.4 Development and application of quantitative methods for measuring
PHF-bound tau 18
2.5 Quantitative studies of tau protein in PHF preparations 21
2.6 Phosphorylation of tau protein 26
2.7 Immunohistochemical studies of altered tau processing in
Alzheimer’s disease 28
2.8 Aetiology of abnormal tau processing in Alzheimer’s disease - insights
from other neurodegenerative disorders 30
2.9 Conclusion 32
References 35
3 Tau proteins and their significance in the pathobiology of
Alzheimer’s disease 41
RM.-K Lee andj? Trrojanowsk
Summary 41
3.1 Introduction 42
V
Contents
3.2 Molecular components of the pathological signatures of Alzheimer’s
disease 44
3.3 Formation of neurofibrillary lesions from derivatized forms of CNS t
(PHFt) in Alzheimer’s disease 47
3.4 Kinases and phosphatases potentially involved in the conversion of
normal CNS t into PHFt in Alzheimer’s disease 50
3.5 Functional implications of neurofibraary lesions in Alzheimer’s disease 51
3.6 Concluding remarks 54
Acknowledgements 54
References 54
4 The genetics of Alzheimer’s disease and mutations in the
amyloid @-proteinp recursor gene 59
E B@ld and A. M. Goak
Summary 59
4.1 Is Alzheimer’s disease a genetic disease? 60
4.2 Clinical and pathological features of Alzheimer’s disease 60
4.3 Other cerebral amyloidoses 61
4.4 Down’s syndrome and Alzheimer’s disease 62
4.5 Linkage to chromosome 2 1 62
4.6 Exclusion of the APP gene 63
4.7 Mutations in the APP gene 64
4.8 Importance of APP mutations in Alzheimer’s disease 69
4.9 Pathogenicity of the APP mutations 70
4.10 Clinical and pathological features associated with APP mutations 71
4.1 1 Linkage of AD to other loci 73
4.12 Conclusions 75
References 75
5 Transcriptional control of the amyloid p-protein precursor
expression 79
W W Quitschke and D. Golkaber
Summary 79
5.1 Cell and tissue distribution of APP and mRNA 80
5.2 APP expression in Alzheimer’s disease 80
5.3 APP expression in Down’s syndrome 80
5.4 APP expression in response to activating factors 81
5.5 Sequence elements of potential regulatory significance in the APP
promoter 82
5.6 Analysis of AF’P promoter regulation 85
5.7 Conclusion 93
Addendum 95
References 96
vi
Contents
6 Post-translational control of the amyloid @-protein
precursor processing 99
J. D. Buxbaum
6.1 Introduction 99
6.2 Protein kinase C and APP 101
6.3 Regulation of APP processing by intracellular messengers 105
6.4 Regulation of APP processing by calcium 107
6.5 Regulation of APP processing in uivo 109
6.6 Summary 110
References 111
7 Processing of the amyloid @-proteinp recursor 115
I: E. GoMe and S. G, rOunkin
7.1 Amyloid and Alzheimer’s disease 115
7.2 A@d eposition in Alzheimer’s disease 116
7.3 @APP 117
7.4 Genetic evidence for a causal role of amyloid deposition in
Alzheimer’s disease 119
7.5 APP processing 121
7.6 Implications for future research on Alzheimer’s disease 132
References 139
8 Neurotoxicity of amyloid p-protein and the amyloid
p-protein precursor 145
X: rOshzkawa
8.1 Introduction 145
8.2 Neurotoxicity of A@a nd related peptides 146
8.3 Neurotoxicity of carboxyl terminal fragments of APP 150
8.4 Neurotoxicity of abnormally metabolized APP fragments 152
8.5 An alternative hypothesis for amyloid-associated neuronal death
inAD 160
8.6 Conclusion 163
References 164
9 Biological functions of the amyloid @-proteinp recursor 167
S. L. Wagner
9.1 Introduction 167
9.2 Characterization and distribution of APP 168
9.3 Potential physiological roles of APP 173
9.4 Conclusions 179
References 180
vii
Contents
10 Cellular and animal models of amyloid P-protein
amyloidosis 183
S. S. Sisodia, D. R. Borchelt and D. L. Pnce
10.1 Introduction 183
10.2 Biology of APP and AP 184
10.3 Animal models of AD 186
Acknowledgements 189
References 189
11 Relationship of plaques and tangles to Alzheimer’s disease
phenotype 193
j! C. Morris
1 1.1 Introduction 193
1 1.2 Clinical phenotype 194
1 1.3 Plaques, tangles and Alzheimer’s disease 200
1 1.4 Clinicopathological correlations in AD 215
1 1.5 Conclusions 217
Acknowledgements 218
References 218
12 Apolipoprotein E and Alzheimer’s disease 225
j! Poi&, j! Xalbantoglu, D. Guillaum and II Bertrand
12.1 Apolipoprotein E 225
12.2 ApoE and LDL receptor: a role in PNS regeneration and CNS
reinnervation 227
12.3 Synaptic remodelling and Alzheimer’s disease: a role for ApoE? 23 1
12.4 Alzheimer’s disease and ApoE4 235
12.5 ApoE4 and neuropathological features 237
12.6 ApoE4 and cholinergic deficits 239
12.7 Conclusion 243
References 243
Index 247
The Color Plates are located between pages 18 and 19.
viii
Contributors
Frank ~hall Saint Louis University School of Medicine, 1402 South Grand
Boulevard, St Louis, MO 63104, USA
PMIHpe Bertrand McGillC entre for Studies in Aging, 6875 LaSalle Boulevard,
Verdun, Quebec, Canada H4H 1R7
David R. Borehelt Neuropathology Laboratorg The Johns Hopkins University
School of Medicine, 720 Rutland Avenue, 558 Ross Research Building, Baltimore,
MD 21205-2196, USA
Frances Basfield Department of Psychiat~, Washington University School of
Medicine, 4940 Children's Place, St Louis, MO 63110, USA
Joseph D. Buxbaum Laboratory of Molecular and Cellular Neuroscience, The
Rockefeller University, New York, NY 10021, USA
Pat~ela Edwards Cambridge Brain Bank Laboratory, University of Cambridge
Clinical School, Department of Psychiat~, MRC Centre, Hills Road, Cambridge
CB2 2QH, UK
Alison M. Goate Department of Psychiat~ Washington University School of
Medicine, 4940 Children's Place, St Louis, MO 63110, USA
Todd E. Golde Divisiono f Neuropathology, Institute of Pathology, Case Western
Reserve Universi~, Cleveland, OH 44106, USA
Dmitry Goldgaber Department of Psychiatry and Behavioral Science,
State University of New York at Stony Brook, Stony Brook, NY 11794-8101,
USA
Daniel Guillaume McGillC entre for Studies in Aging, 6875 LaSalle Boulevard,
Verdun, Quebec, Canada H4H 1R7
Charles R. Harrington Cambridge Brain Bank Laboratory, University of
Cambridge Clinical School, Department of Psychiatry, MRC Centre, Hills Road,
Cambridge CB2 2QH, UK
Robert Lai Cambridge Brain Bank Laboratory, University of Cambridge Clinical
School, Department of Psychiat~ MRC Centre, Hills Road, Cambridge CB2
2oH, tJi
Virginia M.-Y;,Lee Department of Pathology and Laboratory Medicine, Division
of Anatomic Pathologg University of Pennsylvania School of Medicine,
Philadelphia, PA 19104, USA
Raul Mena Cambridge Brain Bank Laboratory, University of Cambridge Clinical
School, Department of Psychiatry, MRC Centre, Hills Road, Cambridge CB2
2QH,
John C. Morris Washington University School of Medicine, 660 South Euclid
Avenue, St Louis, MO 63110, USA
Elizabeth Mukaetova-Ladlnska Cambridge Brain Bank Laboratorg
University of Cambridge Clinical School, Department of Psychiatry, MRC Centre,
Hills Road, Cambridge CB2 2QH, UK
ix