Heterogeneity of Alzheimer’s Disease

204 Pages·1992·4.47 MB·English

by  Z. S. Khachaturian (auth.)

RESEARCH AND PERSPECTIVES IN ALZHEIMER'S DISEASE
Fondation Ipsen
Editor
Yves Christen, Fondation Ipsen, Paris (France)
Editorial Board
Yves Agid, Hopital Piti6 Salpetriere, Paris (France)
Albert Aguayo, The Montreal Hospital, Montreal (Canada)
Luigi Amanducci. University of Florence, Florence (Italy)
Brian H. Anderton, Institute of Psychiatry, London (GB)
Raymond T. Bartus, Cortex, Irvine (USA)
Anders Bjorklund, University of Lund (Sweden)
Floyd Bloom, Scripps Clinic and Research Foundation, La Jolla (USA)
Fram;ois Boller, Inserm U 324, Paris (France)
Carl Cotman, University of California, Irvine (USA)
Peter Davies. Albert Einstein College of Medicine, New York (USA)
Andre Delacourte, Inserm U 16, Lille (France)
Steven Ferris, New York University Medical Center, New York (USA)
Jean-Fram;ois Foncin, Hopital Piti6 Salpetriere, Paris (France)
Franr,;oise Forette, Hopital Broca, Paris (France)
Fred Gage, University of California, La Jolla (USA)
Carleton D. Gajdusek, National Institute of Health, Bethesda (USA)
George G. Glenner, University of California, La Jolla (USA)
Dmitry Goldgaber, State University of New York Stone Brook (USA)
John Hardy, St. Mary's Hospital, Medical School, London (GB)
and University of South Florida, Tampa (USA)
Jean-Jaques Hauw, Hopital Piti6 Salpetriere, Paris (France)
Robert Katzman, University of California, La Jolla (USA)
Claude Kordon, Inserm U 159, Paris (France)
Kenneth K. Kosik, Harvard Medical School Center of Neurological diseases
and Brigham and Women's Hospital. Boston (USA)
Yvon Lamour, Inserm U 161, Paris (France)
Jacques Mallet, CNRS, Gif-sur-Yvette (France)
Colin L. Masters, University of Melbourne, Parkville (Australia)
Stanley 1. Rapoport, National Institute on Aging, Bethesda (USA)
Andre Rascol, Hopital Purpan, Toulouse (France)
Barry Reisberg, New York University Medical Center, New York (USA)
Allen Roses, Duke University Medical Center, Durham (USA)
Dennis 1. Selkoe, Harvard Medical School Center for Neurological Diseases
and Brigham and Women's Hospital, Boston (USA)
Michael L. Shelanski, Columbia University, New York (USA)
Pierre-Marie Sinet, Hopital Necker, Paris (France)
Peter St George-Hyslop, University of Toronto, Toronto (Canada)
Robert Terry, University of California, La Jolla (USA)
Henry Wisniewski, Institute for Basic Research in Development Disabilities,
Staten Island (USA)
Edouard Zarijian, Centre Hospitalier Universitaire, Caen (France)
F. Boller F. Forette Z. Khachaturian
M. Poncet Y. Christen (Eds.)
Heterogeneity of
Alzheimer's Disease
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo Hong Kong
Barcelona Budapest
Boller, Francois, Prof. Dr.
INSERM U324, 2ter rue de Alesia
F-75015 Paris
Forette, F.
Hopital Broca
54 rue Pascal
F-75013 Paris
Khachaturian, Z.S.
National Institute on Aging
National Institutes of Health
Bethesda, MD 20892, USA
Poncet, Michel
Clinique de Neurologie, CHU La Timone
Bd Jean Moulin,
F-13385 Marseille Cedex 05
Christen, Yves, PH. D.
Fondation Ipsen pour La Recherche Therapeutique
30, rue Cambronne
F-75737 Paris CEDEX 15
ISBN-13: 978-3-642-46778-3 e-ISBN-13: 978-3-642-46776-9
DOl: 10.1007/978-3-642-46776-9
This work is subject to copyright. All rights are reserved, whether the whole or part of the material
is concerned, specifically the rights of translation, reprinting, reuse of illustration, recitation,
broadcasting, reproduction on microfilms or in other ways, and storage in data banks. Duplication
of this publication or parts thereof is only permitted under the provisions of the German Copyright
Law of September 9, 1965, in its current version, and a copyright fee must always be paid.
Violations fall under the prescutation act of the German Copyright Law.
© Springer-Verlag Berlin Heidelberg 1992
Softcover reprint of the hardcover 1s t edition 1992
The use of general descriptive names, trade marks, etc. in this publication even if the former are
not especially identifed, is not to be taken as a sign that such names, as understood by the Trade
marks and Merchandise Marks Act, may accordingly be used by anyone.
Product Liability: The publisher can give no guarantee for information about drug dosage and
application thereof contained in this book. In every individual case the respective user must check
its a accuracy by consulting other pharmaceutical literature.
Typesetting: Cicero Lasersatz, 8900 Augsburg
27/314515432 10-Printed on acid-free paper
Preface
This volume contains the proceedings of a symposium held in Marseille on
April 6, 1992, on the topic "Heterogeneity of Alzheimer's disease." This was
the eighth of a continuing and very successful series of meetings related to
Alzheimer's disease organized by the Fondation Ipsen pour la Recherche
Therapeutique. These symposia, known as "Colloques medecine et
recherche," started in 1987 and have dealt with widely different aspects of the
disease such as immunology, genetics, neuronal grafting, biological markers,
imaging, growth factors, and last year's less conventional topic of Neurophilo
sophy and Alzheimer's disease. The next IPSEN symposium dedicatet to Alz
heimer's disease will take place in Lyon on June 21, 1993, and will deal with
"Amyloid protein precursors in development, aging, and alzheimer's disease. " It
is being organized by Konrad Beyreuther, Colin Masters, Marc Trillet, and
Yves Christen.
Until a few years ago, several names were used to refer to the most common
cause of dementia in the elderly. They included such terms as "senile psycho
sis," "organic brain syndrome," and "senile dementia." Following Kraepelin,
the term "Alzheimer's disease" was often restricted to an uncommon condition
starting at a younger age (before 60 or 65 years of age). In 1978, the conclu
sions of a symposium organized by Robert Katzman, Robert Terry, and
Katherine Bick pointed out that there was an "increasing recognition that the
clinical and pathological manifestations are almost identical in the presenium
and in the senium." This and the success in the United States of the Alzheimer
Disease and Related Disorders Association (ADRDA, now called Alzheimer
Association) were among the factors contributing to the much more wide
spread use of the term "Alzheimer's disease" in recent years.
Independently of the nomenclature, it has always been obvious to anyone
dealing with demented patients that there are marked differences among pa
tients. In fact, once we start taking a close look, we find that cases always differ
from one another and that no patient is ever exactly like any other. Does this
symply reflect the variability found in any disease, or does it represent the
expression of different pathological phenomena?
This symposium gathered researchers with backgrounds as different as epide
miology, clinical neurology and geriatrics, neuropsychology, neuropathology,
molecular biology, and genetics. The primary purpose of the meeting was to
provide elements that might allow a rational answer to the question of hetero
geneity of Alzheimer's disease. This question is of great theoretical interest,
VI Preface
but with the appearance of new therapeutic interventions, it may well start
having a very significant practical importance.
The city of Marseille and its neighbor Aix-en-Provence have a long-standing
tradition of academic excellence in many fields including neurology and neuro
sciences and we are indebted to the Mayor of Aix, Dr Jean-Francois Picheral,
who provided a very warm welcome to the participants. Once again, the
organization of the meeting was perfect in all respects, thanks to the efforts of
Mrs. Jacqueline Mervaillie and her colleagues. We also wish to thank the
contributors to this volume, the authors of posters, and all the participants to
the meeting. Our particular gratitude goes to Dr. Zaven Khatchaturian who in
the past several years has significantly contributed to the development of
research on Alzheimer's disease in the United States and other countries. Our
thanks also go to Professor Michel Poncet and Profesor George Serratrice who
kindly acted as session chairs, and to Mary Lynn Gage who provided editorial
assistance.
Fran~ois Boller
Yves Christen
Contents
An Overview of Scientific Issues Associated with the Heterogeneity
of Alzheimer's Disease
Z. S. Khachaturian . . . . . . . . . . . . . . . . . . . . . . . . . 1
A Comparison of Clinical Outcome and Survival in Various Forms
of Alzheimer's Disease
R. Mayeux, Y. Stern, and M. Sana . . . . . . . . . . . . . . . . . 4
Prognostic Implications of Symptomatic Behaviors
in Alzheimer's Disease
H. C. Chui, S. Lyness, E. Sobel, and L. S. Schneider 12
Heterogeneous Disappearance of Knowledge
in Alzheimer's Disease
1. Ora/man ................. . 24
Neuropsychological Aspects of Alzheimer's Disease:
Evidence for Inter- and Intra-Function Heterogeneity
y. loanette, B. Ska, A. Poissant, and R. Beland. 33
Primary Progressive Aphasia:
Sharpening the Focus on a Clinical Syndrome
M.-M. Mesulam and S. Weintraub ..... 43
Therapeutic Drug Trials and Heterogeneity
of Alzheimer's Disease
F. Forette, P. Bert, V. Breuil, and F. Boller 67
Pro and Con for Heterogeneity of Alzheimer's Disease:
A View from an Epidemiologist
L. Amaducci and A. Lippi .......... . 74
Heterogeneity in Familial Alzheimer's Disease
M. N. Rossor, A. M. Kennedy, and S. K. Newman 81
VIII Contents
Molecular Genetic Evidence for Etiologic Heterogeneity
of Alzheimer's Disease
P. H. St George-Hyslop, D. R. Crapper McLachlan, f. L. Haines,
A. Bruni, f.-F. Foncin, W. Lukiw, M. P. Montesi, M. Mortilla,
L. Pinessi, R. f. Polinsky, D. Pollen, I.Rainero, E. Rogaev, S. Sorbi,
R. Tanzi, R. Tupler, and G. Vaula . . . . . . . . . . . . . . . . . . . 88
Alzheimer's Disease: many Aetiologies; one Pathogenesis
f. Hardy . ......................... . 96
Locus Heterogeneity of Alzheimer's Disease
A. Roses, M. Pericak-Vance, M. Alberts, A. Saunders, H. Taylor,
f. Gilbert, C. Schwartz bach, M. Peacock, f. Fink, R. Bhasin,
and D. Goldgaber. . . . . . . . . . . . . . . . . . . . . . . . . . 101
Familial Alzheimer's Disease in Germans from Russia:
A Model of Genetic Heterogeneity in Alzheimer's Disease
T. D. Bird, E. M. Nemens, D. Nochlin, S. M. Sumi, E. M. Wijsman,
and G. D. Schellenberg. . . . . . . . . . . . . . . . . . . . . . . .. 118
Protein Phosphorylation Regulates Processing
of the Alzheimer BIA4-Amyloid Precursor Protein
S. E. Gandy, G. L. Caporaso, T. V. Ramabhadran, f. D. Buxbaum,
T. Suzuki, C. Nordstedt, K. Iverfeldt, A. f. Czernik, A. C. Nairn,
and P. Greengard . . . . . . . . . . . . . . . . . . . . . . . . . . . 130
Alzheimer's Disease and Neuroanatomy: Hypotheses and Proposals
C. Duyckaerts, P. Delaere, and i.-i. Hauw ............. 144
Distribution of Tau-PHF in Brodmann Areas Reveals
a Heterogeneity of the Degenerating Process in Rostro-Caudal Regions
and as a Function of Age
P. Vermersch, B. Frigard, A. Wattez, and A. Delacourte . . . . . . .. 156
Alzheimer's Disease and Age-Related Pathology
in Diffuse Lewy Body Disease
D. W. Dickson, E. Wu, H. A. Crystal, L. A. Mattiace, S.-H. C. Yen,
and P. Davies 168
Subject Index 187
Contributors
Alberts, M.
Joseph and Kathleen Bryan Alzheimer's Disease Research Center,
Duke University Medical Center, Durham, MC 27710, USA
Amaducci, L.
Department of Neurologic and Psychiatric Sciences, University of Florence,
Viale Morgagni 85, 50134 Florence, Italy
Biland, R.
Laboratoire TMophile-Alajouanine, C. H. C6te-des-Neiges,
4565, chemin de la Reine-Marie, Montreal, Quebec H3W 1W5, Canada
Bert, P.
H6pital Broca, 54 rue Pascal, 75013 Paris, France
Bhasin, R.
Department of Psychiatry, State University of New York at Stony Brook,
Stony Brook, NY 11794-8101, USA
Bird, T. D.
Departments of Medicine and Pathology, University of Washington Medical
School and the VA Medical Center, Seattle, WA 98018, USA
Boller, F.
INSERM U324, 2ter rue d'Alexia, 75014 Paris, France
Breuil, V.
H6pital Broca, 54 rue Pascal, 75013 Paris, France
Bruni, A.
SMID-SUD, Scala 4, via dei Campione,
Lamezzia Terme, CZ, Italy
Buxbaum, 1. D.
Laboratory of Molecular and Cellular Neuroscience,
The Rockefeller University,
1230 York Avenue, New York, NQ 10021, USA
X Contributors
Caporaso, G. L.
Laboratory of Molecular and Cellular Neuroscience,
The Rockefeller University,
1230 York Avenue, New York, NY 10021, USA
Chui, H. C.
University of Southern California School of Medicine, Los Angeles
and Geriatric Neurobehavior and Alzheimer Center, 12838 Erickson Street,
Downey, CA 90242, USA
Crapper McLachlan, D. R.
Department of Medicine, Centre for Research in Neurodegenerative
Disease, Tanz Neuroscience Building, Univesity of Toronto,
Ontario M5S1A8, Canada
Crystal, H. A.
Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx,
NY 10461, USA
Czernik, A. I.
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller
University, 1230 York Avenue, New York, NY 10021, USA
Davies, P.
Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx,
NY 10461, USA
Delacourte, A.
INSERM U 156, Place de Verdun, 59045 Lille CEDEX, France
Delaere, P.
Laboratoire de Neuropathologie R. Escourolle, Hopital de la Salpetriere,
47, Boulevard de l'Hopital, 75651 Parix CEDEX 13, France
Dickson, D. W.
Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx,
NY 10461, USA
Duyckaerts, C.
Laboratoire de Neuropathologie R. Escourolle, Hopital de la Salpetriere,
47, Boulevard de l'Hopital, 75651 Paris CEDEX 13, France
Fink, I.
Department of Neurology, University of Michigan Medical Center,
Ann Arbor, MI 48104, USA
Foncin, I-F.
Laboratoire de Neurohistologie, Ecole Pratique des Hautes Etudes,
Hopital de la Salpetriere, 75651 Paris CEDEX 13, France