RESEARCH AND PERSPECTIVES IN ALZHEIMER'S DISEASE

Fondation Ipsen

Editor

Yves Christen, Fondation Ipsen, Paris (France)

Editorial Board

Yves Agid, Hopital PitieS Salpetriere, Paris (France) Albert Aguayo, The Montreal General Hospital, Montreal (Canada) Brian H. Anderton, St George's Hospital Medical School, London (GB) Raymond T. Bartus, Cortex, Irvine (USA) Anders Bjorklund, University of Lund (Sweden) Floyd Bloom, Scripps Clinic and Research Foundation, La Jolla (USA) Franr,;ois Boller, Inserm U324, Paris (France) Peter Davies, Albert Einstein College of Medicine, New-York (USA) Andre Delacourte, Inserm U16, Lille (France) Steven Ferris, New-York University Medical Center, New-York (USA) Jean-Franr,;ois Foncin, H6pital PitieS Salpetriere, Paris (France) Franr,;ois Forette, H6pital 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, Stony Brook (USA) John Hardy, St Mary's Hospital, Medical School, London (GB) Jean-Jaques Hauw, Hopital PitieS Salpetriere, Paris (France) Robert Katzman, University of California, La Jolla (USA) Claude Kordon, Inserm U159 Paris (France) Yvon Lamor, InsermU161, Paris (France) Jacqes Mallet, CNRS, Gif-sur-Yvette (France) Colin L. Masters, University of Melbourne, Parkville (Australia) Stanley I. Rapoport, National Institute on Aging, Bethesda (USA) Andre Rascol, H6pital Purpan, Toulouse (France) Barry Reisberg, New York University Medical Center, New York (USA) Dennis J. Selkoe, Harvard Medical School Center for Neurological Diseases

and Brigham and Women's Hospital, Boston (USA) Michael L. Shelanski, Columbia University, New-York (USA) Jean-Louis Signoret, H6pital PitieS Salpetriere, Paris (France) Pierre-Marie Sinet, Hopital Necker, Paris (France) Peter St George Hyslop, Massachussetts General Hospital, Boston (USA) Henry Wisniewski, Institute for Basic Research in Development Disabilities,

Staten Island (USA) Edouard Zarifian, Centre Hospitalier Universitaire, Caen (France).

F. Boller R. Katzman A. Rascol J.-L. Signoret Y. Christen (Eds.)

Biological Markers of Alzheimer's Disease

Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Hong Kong

Boller, Fran<;ois, Prof. Inserm U324 2 ter, rue d' Alesia 75014 Paris, France

Katzman, Robert, Prof. University of California at San Diego La Jolla, USA

Rascol, Andre, Prof. Hopital Purpan Toulouse, France

Signoret, Jean-Louis, Prof. Hopital Salpetriere, Paris, France

Christen, Yves, Dr. Fondation IPSEN pour la Recherche Therapeutique, 30, rue Cambronne, F-75737 Paris Cedex

ISBN-13: 978-3-642-46692-2 001: 10.1007/978-3-642-46690-8

e-ISBN-13: 978-3-642-46690-8

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© Springer-Verlag Berlin Heidelberg 1989 Softcover reprint ofthe hardcover 1 st edition 1989

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Preface

This volume presents the proceedings of the symposium held in Toulouse on April 24, 1989, on the topic "Biological Markers of Alzheimer's Disease." This sym­posium was the fourth of a continuing and successful series of Colloques Medecine et Recherche organized by the Fondation IPSEN pour la Recherche Therapeutique, addressing various aspects of contemporary research in the field of Alzheimer's disease (AD). The series started in September 1987 with "Im­munology and Alzheimer's Disease," followed 6 months later in Paris by "Gene­tics and Alzheimer's Disease" and in September 1988 in Montpellier by "Neuronal Grafting and Alzheimer's Disease."

The present symposium was organized for the purpose of gathering the most current ideas concerning biological markers of AD. The papers presented at this symposium may be roughly subdivided into three groups. The first deals with the markers of AD at the level of the brain itself. These markers are studied either through the cerebrospinal fluid or through techniques such as nuclear magnetic resonance (NMR) - approaches which respectively aim at demonstrating the cerebral changes indicated by the debris resulting from the disease, or studying the possible neurochemical abnormalities that occur in the earlier stages of AD. The second group of papers deals with possible extraneuronal changes in the blood, in the skin, or in other organs of AD patients, while the third group addresses the most current research on the genetic abnormalities which may be found in AD subjects. We think that the papers gathered in this volume will provide a unique view of the state of the art of these aspects of AD and their relation to both the pathogenesis and the in vivo diagnosis of the disease.

The city of Toulouse where this symposium was held has a long tradition of research in neuroscience, neurology and geriatrics. We wish to thank the Dean of the Faculty of Medicine, Professor Guiraud-Chaumeil, who generously provided hospitality in his prestigious insitution. We also wish to express our gratitude to the Institut National de la Sante et de la Recherche Medicale (INSERM) for kindly agreeing to sponsor this meeting. We also wish to thank Mrs Mary Lynn Gage for her editorial assistance, Mrs Jacqueline Mervaillie for the organization of the meeting, and Yves Agid for his collaboration as chairman of the meeting.

The next meeting was organized in Lille on October 16,1989 and was devoted to "Imaging, Cerebral Topography and Alzheimer's Disease."

Francois Boller Yves Christen

Contents

Cerebrospinal Fluid Neurochemical Markers in Alzheimer's Disease J. R. Atack ............................ . 1

Potential Diagnostic Markers for Alzheimer's Disease P. Davies ...................... . 17

Cerebrospinal Fluid-Based Laboratory Test for Alzheimer's Disease H. M. Wisniewski, P. D. Mehta, K. S. Kim, and G. S. Merz . . .. .... 23

Probes for the Molecular Components of Plaques and Tangles Point to a Broadening View of Alzheimer Pathology K. S. Kosik and D. J. Selkoe . . . . . . . . . . . . . . . . . . . . . 30

Tau 64 and Tau 69: Two Early Biochemical Markers of Neurofibrillary Degeneration A. Delacourte, S. Flament, A. De!ossez, L. Buee, B. Heman, M. Parent, A. Furby, D. Leys, M. Goudemand, A. Destee, and H. Petit .... 39

A cDNA Encodes Epitopes Shared Between Microtubule-Associated Protein MAP2 and Alzheimer Neurofibrillary Tangles: In Situ Hybridization and Immunocytochemistry J. P. Brion, A. M. Couck, M. E. Cheetham, D. Hanger, B. H. Anderton, andJ. Flament-Durand . . . . . . . . . . . . . . . . . . . . . . .. .... 56

Epitopes Characteristic of Paired Helical Filaments Demonstrated in Microglial Cells and Macrophages of the Meninges: A Possible Laboratory Diagnosis of Alzheimer's Disease from Cerebrospinal Fluid? J. Ulrich, S. Ipsen, A. Probst, and J. P. Brion . . . . . . . . . . . . . 66

Relationship Between Tau, Paired Helical Filaments, Amyloid and the Intellectual Deterioration in the Neocortex in Normal Aging and in Senile Dementia of the Alzheimer Type P. Delaere, C. Duyckaerts, J. P. Brion, F. Piette, and J. -J. Hauw . .. 73

Molecular Insights into Alzheimer's Disease J. W. Pettegrew . . . . . . . . . . . . . . . 83

VIII Contents

Altered Protein Kinase and Amyloid p-Protein Precursor in Alzheimer's Disease: Which Comes First? T. Saitoh and D. S. Iimoto . . . . . . . . . . . . . . . . . . . . .. .... 105

The Amyloid Gene of Alzheimer's Disease and Neuronal Dysfunction J. M. Salbaum, C. L. Masters, and K. Beyreuther . . . . . . . . .. ... 118

Cloning of Different Amyloid Peptide Precursors from Brains of Patients with Alzheimer's Disease F.de Sauvage, A. F. Macq, J. M. Maloteaux, and J. N. Octave ..... .. 123

Genetic Studies of the Alzheimer's Disease-Associated Amyloid p-Protein Precursor Gene and Familial Alzheimer's Disease R. E. Tanzi, P. St. George-Hyslop, M. James, J. L. Haines, andJ. F. Gusella 130

Alzheimer's Disease and Chromosome 21 A. R. Haynes, M. J. Owen, A. M. Goate, L. A. James, M. J. Mullan, R. Williamson, P. Roques, M. N. Rossor, and J. A. Hardy . . . . . . 138

'Calcium and the Cytoskeleton in Alzheimer's Disease M. L. Shelanski . . . . . . . . . . . . . . . . . . . .

Use of Cultured Skin Fibroblasts in Studies of Alzheimer's Disease

....... 146

J. P. Blass, A. C. Baker, K.-F. R. Sheu, L. Ko, R. S. Black, andA. Smith .. 153

Lactate Production and Glycolytic Enzymes in Skin Cultured Cells from Alzheimer's Disease Patients S. Sorbi, M. Mortilla, S. Piacentini, G. Tesco, S. Tonini, and L. Amaducci 163

Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 167

Contributors

Amaducci, L. Department of Neurology and Psychiatry, University of Florence, Italy Viale Morgagni 85,1-50134 Florence, Italy

Anderton, B. H. Department of Immunology, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK

Atack,l. R. Laboratory of Neurosciences, National Institute on Aging, 9000 Rockville Pike, Bethesda, MD 20892, USA

Baker, A. C. The Burke Rehabilitation Center, 785 Mamaroneck Avenue, White Plains, NY 10605, USA

Beyreuther, K. Zentrum rur Molekulare Biologie, Universitat Heidelberg, 1m Neuenheimer Feld 282, D-69oo Heidelberg, FRG

Black, R. S. The Burke Rehabilitation Center, 785 Mamaroneck Avenue, White Plains, NY 10605, USA

Blass,l. P. The Burke Rehabilitation Center, 785 Mamaroneck Avenue, White Plains, NY 10605, USA

Brion,l. P. Laboratoire d' Anatomie Pathologique, Universite Libre de Bruxelles. Campus Erasme, 808, route de Lennik, B-1070 Bruxelles, Belgium

Buee, L. Laboratoire de Neurosciences, Unite INSERM no. 16, Faculte de Medecine de Lille, F-59045 Lille Cedex, France

X Contributors

Cheetham, M. E. Department of Immunology, St. George's Hospital Medical School. Cranmer Terrace, London SW17 ORE, UK

Couck, A. M. Laboratoire d' Anatomie Pathologique, Universite Libre de Bruxelles. Campus Erasme, 808, route de Lennik, B-1070 Bruxelles, Belgium

Davies, P. Departments of Pathology and Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA

De!ossez, A. AD.E.R.M.A, Faculte de Medecine, F-59045 Lille Cedex, France

Delacourte, A. Laboratoire de Neurosciences, Unite INSERM no. 16, Faculte de Medecine de Lille, F-59045 Lille Cedex, France

Delaere, P. Laboratoire de Neuropathologie R. Escourolle. Hopital Pitie- Salpetriere, 47 Bd de l'Hopital, F-75013 Paris, France

Destee, A. AD.E.R.M.A, Faculte de Medecine, F-59045 Lille Cedex, France

Duyckaerts, C. Laboratoire de Neuropathologie R. Escourolle. Hopital Pitie- Salpetriere, 47 Bd de l'Hopital, F-75013 Paris, France

Flament, S. Laboratoire de Neurosciences, Unite INSERM no. 16, Faculte de Medecine de Lille, F-59045 Lille Cedex, France

Flament-Durand,l. Laboratoire d' Anatomie Pathologique, Universite Libre de Bruxelles. Campus Erasme, 808, route de Lennik, B-1070 Bruxelles, Belgium

Furby, A. AD.E.R.M.A, Faculte de Medecine, F-59045 Lille cedex, France

Goate, A. M. Alzheimer's Disease Research Group, Departments of Biochemistry and Neurology, St. Mary's Hospital Medical School, London W21PG, UK

Goudemand, M. AD.E.R.M.A, Faculte de Medecine, F-59045 Lille cedex, France

Contributors XI

Gusella, f. F. The Neurogenetics Laboratory, Massachusetts General Hospital, Boston, MA02114, USA

Haines, f. L. The Neurogenetics Laboratory, Massachusetts General Hospital, Boston, MA02114, USA

Hanger, D. Department of Immunology, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK

Hardy, f. A. Alzheimer's Disease Research Group, Departments of Biochemistry and Neurology, St. Mary's Hospital Medical School, London W21PG, UK

Hauw, f.-f. Laboratoire de Neuropathologie R. Escourolle. Hopital Pitie- Salpetriere, 47 Bd de l'Hopital, F-75013 Paris, France

Haynes, A. R. Alzheimer's Disease Research Group, Departments of Biochemistry and Neurology, St. Mary's Hospital Medical School, London W2 lPG, UK

Hernon, B. Laboratoire de Neurosciences, Unite INSERM no. 16, Faculte de Medecine de Lille, F-59045 Lille Cedex, France

Iimoto, D. S. University of California, San Diego, School of Medicine, Department of Neurosciences, M-024 and Center for Molecular Genetics, La Jolla, CA 92093, USA

Ipsen, S. Neuropathology Division, Department of Pathology, University of Basel, CH-4003 Basel, Switzerland

fames, L. A. Alzheimer's Disease Research Group, Departments of Biochemistry and Neurology, St. Mary's Hospital Medical School, London W2 lPG, UK

fames, M. The Neurogenetics Laboratory, Massachusetts General Hospital, Boston, MA 02114, USA

XII Contributors

Kim, K. S. New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA

Ko, L. The Burke Rehabilitation Center, 785 Mamaroneck Avenue, White Plains, NY 10605, USA

Kosik, K. S. Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA

Leys, D. A.D.E.R.M.A., Faculte de Medecine, F-59045 Lille C6dex, France

Macq,A. F. Universite Catholique de Louvain, Laboratoire de Neurochimie, Avenue Hippocrate 10, B-1200 Bruxelles, Belgium

Maloteaux, J. M. Universite Catholique de Louvain, Laboratoire de Neurochimie, Avenue Hippocrate 10, B-1200 Bruxelles, Belgium

Masters, C. L. Department of Pathology, University of Melbourne, Parkville, Victoria 3502, Australia

Mehta, P. D. New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA

Merz, G. S. New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA

Mortilla, M. Department of Neurology and Psychiatry, University of Florence, Viale Morgagni 85, 1-50134 Florence, Italy

Mullan, M. J. Alzheimer's Disease Research Group, Departments of Biochemistry and Neurology, St. Mary's Hospital Medical School, London W21PG, UK

Octave, J. N. Universite Catholique de Louvain, Laboratoire de Neurochimie, Avenue Hippocrate 10, B-1200 Bruxelles, Belgium

Contributors XIII

Owen, M.J. Alzheimer's Disease Research Group, Departments of Biochemistry and Neurology, St. Mary's Hospital Medical School, London W2 1PG, UK

Parent, M. AD.E.R.M.A, Faculte de Medecine, F-59045 Lille Cedex, France

Petit, H. AD.E.R.M.A, Facu1te de Medecine, F-59045 Lille Cedex, France

Pettegrew, J. W. University of Pittsburgh, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, Pittsburgh, PA 15213-2593, USA

Piacentini, S. Department of Neurology and Psychiatry, University of Florence, Viale Morgagni 85, 1-50134 Florence, Italy

Piette, F. Hopital Charles Foix, 7 Avenue de la Republique, F-94205 Ivry, France

Probst, A. Neuropathology Division, Department of Pathology, University of Basel, CH-4003 Basel, Switzerland

Roques, P. Alzheimer's Disease Research Group, Departments of Biochemistry and Neurology, St. Mary's Hospital Medical School, London W21PG, UK

Rossor, M. N. Alzheimer's Disease Research Group, Departments of Biochemistry and Neurology, St. Mary's Hospital Medical School, London W21PG, UK

Saitoh, T. University of California, San Diego, School of Medicine, Department of Neurosciences, M-024 and Center for Molecular Genetics, La Jolla, CA 92093, USA

Salbaum, J. M. Zentrum rur Molecular Biologie, Universitiit Heidelberg, 1m Neuenheimer Feld 282, D-6900 Heidelberg, FRG

de Sauvage, F. Universite Catholique de Louvain, Laboratoire de Neurochimie, Avenue Hippocrate 10, B-1200 Bruxelles, Belgium

XIV Contributors

Selkoe, D. I. Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA

Shelanski, M. L.

Department of Pathology and Center for Neurobiology and Behaviour, College ofPhysicans and Surgeons, Columbia University, New York, NY 10032, USA

Sheu, K.-F. R. The Burke Rehabilitation Center, 785 Mamaroneck Avenue, White Plains, NY 10605, USA

Smith, A. The Burke Rehabilitation Center, 785 Mamaroneck Avenue, White Plains, NY 10605, USA

Sorbi, S. Department of Neurology and Psychiatry, University of Florence, Viale Morgagni 85, 1-50134 Florence, Italy

St. George-Hyslop, P. The Neurogenetics Laboratory, Massachusetts General Hospital, Boston, MA 02114, USA

Tanzi, R. E. The Neurogenetics Laboratory, Massachusetts General Hospital, Boston, MA02114, USA

Tesco, G. Department of Neurology and Psychiatry, University of Florence, Viale Morgagni 85,1-50134 Florence, Italy

Tonini, S. Department of Neurology and Psychiatry, University of Florence, Viale Morgagni 85, 1-50134 Florence, Italy

Ulrich, I. Neuropathology Division, Department of Pathology, University of Basel, CH-4003 Basel, Switzerland

Williamson, R. Alzheimer's Disease Research Group, Departments of Biochemistry and Neurology, St. Mary's Hospital Medical School, London W21PG, UK

Contributors XV

Wisniewski, H. M. New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA