Genetics and Alzheimer’s Disease

197 Pages·1988·4.38 MB·English

by  B. H. Anderton (auth.)

RESEARCH AND PERSPECTIVES IN ALZHEIMER'S DISEASE
Fondation Ipsen
Editor
Yves Christen, Fondation Ipsen, Paris (France)
Editorial Board
Yves Agid, Hopital Pitie 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, American Cyanamid, Pearl River (USA)
Floyd Bloom, Scripps Clinic and Research Foundation, La Jolla (USA)
Fran~ois Boller, University of Pittsburgh School of Medicine, Pittsburgh (USA)
Andre Delacourte, Inserm U16, Lille (France)
Steven Ferris, New-York University Medical Center, New-York (USA)
Jean-Fran~ois Foncin, Hopital Salpetriere, Paris (France)
Fran~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, National Institute of Health, Bethesda (USA)
John Hardy, St Mary's Hospital, Medical School, London (GB)
Jean-Jacques Hauw, Hopital Pitie Salpetriere, Paris (France)
Claude Kordon, Inserm U159, Paris (France)
Yvon Lamour, Inserm U161, Paris (France)
Jacques Mallet, CNRS, Gif-sur-Yvette (France)
Colin L. Masters, Royal Perth Hospital, Perth (Australia)
Stanley l. Rapoport, National Institute on Aging, Bethesda (USA)
Andre Rascol, Hopital 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)
Jean-Louis Signoret, Hopital 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 Developmental Disabilities,
Staten Island (USA)
Edouard Zarifian, Centre Hospitalier Universitaire, Caen (France).
P. M. Sinet Y. Lamour Y. Christen (Eds.)
Genetics
and Alzheimer's Disease
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Sinet, Pierre Marie, Dr.
Laboratoire de Biochimie Genetique
Lamour, Yvon, Dr.
INSERM U161, 75014 Paris, France
Christen, Yves, Dr.
Fondation IPSEN
pour la Recherche Therapeutique
30, rue Cambronne
75737 Paris Cedex, France
ISBN-13: 978-3-642-73649-0 e-ISBN-13: 978-3-642-73647-6
DOl: 10. 1007/978-3-642-73647-6
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Preface
This volume contains the proceedings of the meeting Genetics and Alzheimer's Disease
held in Paris, on March 25,1988, by the Fondation Ipsen pour la Recherche Therapeuti
que. This meeting was the second of the series of Colloques Medecine et Recherche devoted
to Alzheimer's disease. The first one was held in Angers (France) on September 14, 1987;
the proceedings of this meeting have already been published and are entitled Immunology
and Alzheimer's Disease (1988, edited by A Pouplard-Barthelaix, J Emile, and Y
Christen). The third Colloque Medecine et Recherche, organized in Montpellier on Sep
tember 19, 1988, dealt with neuronal grafting; the proceedings of this last meeting will be
published in early 1989 (Neuronal Grafting and Alzheimer's Disease: Future Perspectives,
edited by F Gage, A Privat and Y Christen).
In each case, the Fondation Ipsen deliberately focuses attention on the most up-to-date
themes, and sometimes the most controversial ones, from medical and scientific research.
The genetic aspects of Alzheimer's Disease (AD) stands at the very forefront of research
carried out in the last 2 years. It complements research using the formal approach, which
has become possible thanks to the study of extended kindreds by J-F Foncin and other
scientists.
The recent work on molecular and genetics biology has followed two main pathways:
1. The study of the gene(s) responsible for the familial form(s), which can be considered
the AD gene(s). Several papers published in 1987 locate a gene of this type on
chromosome 21. This location appears very interesting as (a) the question of the
relationship between AD and Down's syndrome (trisomy 21) has been discussed for
many years and (b) the gene encoding the precursor of the amyloid A4 protein or ~
protein (major component of senile plaques) is also located on chromosome 21, as
several groups demonstrated in 1987.
During this meeting of the Fondation Ipsen, researchers from Durham presented their
findings, which indicated that the gene implicated in familial late-onset AD is not
located on chromosome 21. More recently, scientists from Seattle have published other
results also excluding chromosome 21 (Schellenberg GD, Bird TD, Wijsman EM,
Moore DK, Boehnke M, Bryant EM, Lampe TH, Nochlin D et al.: Science, 1988,242:
1507-1510). Therefore, it seems quite possible that AD may be an heterogenous
disease and that, even for the familial forms, several loci located on different chromo
somes are involved.
2. The amyloid A4 protein precursor (APP) gene. According to several authors, the
amyloid formation (i.e., the A4 protein deposition) could be a crucial event for the
clinical expression of dementia. Recent work on molecular genetics of APP gives a
VI Preface
better understanding of its function as a membrane protein probably involved in cell
contact.
Morever, the finding in 1988 of longer forms of APP carrying an additional domain with
protease inhibitor function raises a number of questions about this kind of protein. Some
protease inhibitors are thought to control neurite extension. Therefore it is possible that
longer forms of APP could control protease-dependant processes required for brain
plasticity (and also tissue regeneration since the corresponding mRN As are found not only
in the brain but also in peripheral organs).
Thus, as we can see, all of this work not only provides a better understanding, of the
mapping of the human genome, but also demonstrates a new approach - at the molecular
level-about how to go from the gene to the lesion and to the disease. This is the main goal
of the work described and gathered in this book.
The editors wish to thank Mrs. Mary Gage for her editorial assistance, Mrs. Jacqueline
Mervaillie for the organization of the meeting in Paris, an Yves Agid, Claude Kordon, and
Jacques Mallet for their collaboration as chairmen of the meeting.
Yves Christen
Vice-President of the Fondation Ipsen pour la Recherche Therapeutique
Contents
The Genetics of Alzheimer's Disease: Current Status and Future Development
of Research
B. H. Anderton. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Heterogeneity in Alzheimer's Disease: An Exercise in the Resolution
of a Phenotype
M. F. Folstein, A. Warren, andP. C. McHugh. . . . . . . . . . . . . . . . . . . . . . . . 5
Extended Kindreds as a Model for Research on Alzheimer's Disease
J.-F. Foncin, D. Salmon, andA. C. Bruni. . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Familial Aggregation of Dementia of Alzheimer Type:
Analysis from an Epidemiological Point of View
A. Alperovich, and C. Berr. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31
The IMAGE Project: A Geographical Laboratory for the Integration
of Multidisciplinary Data
D. Gauvreau, R. Bouchard, S. Gauthier, J. Mathieu, C. Boily, A. Cholette,
Y. Robitaille, P. Bouchard, N. Bouchard, L.-P. Doyon, M. Gaudreault, A. Ouellet,
M. Dumont, P. Kishka, C. Fournier, J. Nalbantoglu, G. Lacoste-Royal,
D. Gautrin, S. Froda, M. de Braekeleer, G. Bouchard, andJ. Mortimer . . . . . . . . 40
Dermatoglyphic Patterns in Senile Dementia of Alzheimer's Type
N. Okra Podrabinek, M. Roudier, Y. Lamour, and J. de Grouchy 51
A Phylogenetic Hypothesis for Alzheimer's Disease
S.l. Rapoport. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Chromosome 21, Trisomy 21, and Alzheimer's Disease
P.-M. Sinet, Z. Rahmani, J.-L. Blouin, A. Nicole, O. Ceballos, N. Creau-Goldberg,
C. Turleau,l. de Grouchy,l.-L. Huret, M. Poissonnier, and J.-M. Delabar 89
Trisomic and Transgenic Mice in the Study of the Pathogenesis
of Alzheimer's Disease and Down's Syndrome
C. J. Epstein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
VIII Contents
Molecular Genetic Strategies in Familial Alzheimer's Disease:
Theoretical and Practical Considerations
P. H. St George-Hyslop, L. Farrer, J. Haines, R. Myers, R. Polinsky, L. Nee,
A Bruni, S. Sorbi, S. Piacentini, L. Amaducci, J.-F. Foncin, R. G. Feldmann,
P. Frommelt, P. Watkins, R. Tanzi, J. Aalbo, J. Growdon, D. Drachman,
D. Pollen, P. M. Conneally, andJ. Gusella . . . . . . . . . . . . . . . . . . . . . . . . .. 109
Genetic Linkage Studies in Late-Onset Alzheimer's Disease Families
M.A. Pericak-Vance, L. H. Yamaoka, C. S. Haynes, J. L. Haines, P. C. Gaskell,
W.-Y. Hung, C.M. Clark, AL. Heyman, J.A. Trofatter, J.P. Eisenmenger,
J. R. Gilbert, J. E. Lee, M. J. Alberts, M. C. Speer, D. V. Dawson, R. J. Bartlett,
N. L. Earl, T. Siddique, and A D. Roses .. . . . . . . . . . . . . . . . . . . . . . . . .. 116
Genetic Linkage Analysis in Two Large Belgian Alzheimer's Families
with Chromosomes 21 DNA Markers
C. van Broeckhoven, W. ·van Hul, W. Backhovens, P. Raeymaekers, G. van Camp,
P. Stinissen, A Wehnert, G. de Winter, J. Gheuens, andA Vandenberghe ...... 124
Alternative cDNA Clones of Amyloid ~-Protein Precursor Gene Encode
Proteinase Inhibitor
D. Goldgaber,J. W. Teener, andD. C. Gajdusek . . . . . . . . . . . . . . . . . . . . .. 130
Precursor of Alzheimer's Disease (PAD) A4 Amyloid Protein
C. L. Masters, G. Multhaup, J. M. Salbaum, A Weidemann, T. Dyrks, C. Hilbich,
P. Fischer, G. Konig, J. Beer, D. Bunke, U. Manning, S. Fuller, R. Martins,
G. Simms, B. Rumble, and K. Beyreuther . . . . . . . . . . . . . . . . . . . . . . . . .. 134
Cloning of the Beta Amyloid Peptide Gene in Alzheimer's Disease
J. N. Octave, F. de Sauvage, A. F. Macq, J. M. Maloteaux, C. G. Rasool,
M. P. Vitek, A J. Blume, J. M. Brucher, T. de Barsy, A Trouet, and E. C. Laterre.. 142
Molecular Analysis of Patients with Alzheimer's Disease
J.-M. Delabar, Z. Rahmani, J.-L. Blouin, A Nicole, N. Creau-Goldberg,
l. Ceballos, Y. Lamour, M. Roudier, P. Davous, andP.-M. Sinet . . . . . . . . . . .. 151
Paired Helical Filaments (PHFs): Update 1988
H. M. Wisniewski, and K. Iqbal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 157
Studies of the Beta-Amyloid Precursor Protein in Brain and the Pathological
Transformation of Tau into the Neurofibrillary Tangle
K. S. Kosik, andD.J. Selkoe. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 164
Etiology Versus Pathogenesis: The Causes of Post-Translational Modifications
of Host-Specified Brain Proteins to Amyloid Configuration
D. C. Gajdusek . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 174
SubjectIndex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 177
Contributors
Aalbo, J.
Massachussetts General Hospital and Harvard Medical School, Boston,
MA 02114, USA
Alberts, M.J.
Department of Medicine, Division of Neurology , Duke University Medical Center,
Durham, NC 27710, USA
Alperovitch, A.
INSERM, U. 169, 16, avenue P. V. Couturier, 94807 Villejuif Cedex, France
Amaducci, L.
Instituto di Mallatie Nervose e Mentali, University of Florence, Florence, Italia
Anderton, B. H.
Department ofImmunology, St. George's Hospital, Medical School, Cranmer Terrace,
London SW17 ORE, UK
Backhovens, H.
University of Antwerp (U .LA.), Departments of Biochemistry and Neurology,
Ghent, Belgium
de Barsy, T.
Universite Catholique de Louvain, Laboratoire de Neurochimie UCL 1352,
Av. Hippocrate 10, B 1200, Bruxelles, Belgium
Bartlett, R. J.
Department of Medicine, Division of Neurology , Duke University Medical Center,
Durham, NC 27710, USA
Beer, J.
Centerfor Molecular Biology, University of Heidelberg , 1m Neuenheimer Feld 282,
6900 Heidelberg 1, W. -Germany
Berr, C.
INSERM, U 169, 16, avenue P. V. Couturier, 94807 Villejuif Cedex, France
X Contributors
Beyreuther, K.
Center for Molecular Biology, University of Heidelberg, 1m Neuenheimer Feld 282,
6900 Heidelberg 1, W.-Germany
Blouin, I. -L.
Laboratoire de Biochimie Genetique, Hopitai Necker, 75015 Paris, France
Blume, A.I.
Lederle Laboratories, Pearl River, 10965 New York, USA
Boily, C.
Hopital de Chicoutimi, Chicoutirni, Canada
Bouchard, G.
a
SOREP, Universite du Quebec Chicoutimi, Chicoutimi, Canada
Bouchard, N.
Hopital de la Baie, La Baie, Canada
Bouchard, P.
Hopital de Jonquiere, Jonquiere, Canada
Bouchard, R.
Hopital de l'Enfant-Jesus, Quebec, Canada
de Braekeleer, M.
a
SOREP, Universite du Quebec Chicoutimi, Chicoutirni, Canada
v. Broeckhoven, C.
University of Antwerp (U .I.A.), Departments of Biochemistry and Neurology,
Ghent, Belgium
Brucher, I. M.
Universite Catholique de Louvain, Laboratoires de Neurochimie UCL 1352,
Avenue Hippocrate 10, B. 1200, Bruxelles, Belgium
Bruni, A. C.
Servizio di Neurologia, USL 17, e Projetto SMID-SUD, Lamezia Terme, Italia
Bunke, D.
Center for Molecular Biology, University of Heidelberg, 1m Neuenheimer Feld 282,
6900 Heidelberg 1, W. Germany
v. Camp, G.
University of Antwerp (U.I.A.), Departments of Biochemistry and Neurology,
Ghent, Belgium
Contributors XI
Ceballos, 1.
Laboratoire de Biochemie Genetique, Hopital Necker, 149 rue de Sevres,
75015 Paris, France
Cholette, A.
Hopital de Chicoutimi, Chicoutimi, Canada
Clark, C.M.
Department of Medicine, Division of Neurology, Duke University Medical Center,
Durham, NC 27710, USA
Conneally, P. M.
Clinical Neuropharmacology Section, Medical Neurology, Branch National Institute of
Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892, USA
Creau-Goldberg, N.
INSERM U 173, CNRS, Hopital Necker - Enfants Malades, 149, rue de Sevres,
75743 Paris, Cedex 15, France
Davous, P.
Hopital d' Argenteuil, 95107 Argenteuil, France
Dawson, D. V.
Department of Community and Family Medicine, Division ofBiometry and Medical
Informatics, Duke University Medical Center, Durham, NC 27710, USA
Delabar, J.-M.
Laboratoire de Biochimie Genetique, Hopital Necker, 149 rue de Sevres,
75014 Paris, France
Doyon, L.-P.
Hopital de Roberval, Roberval, Canada
Drachman, D.
Department of Neurology, University of Massachussetts Medical School and University
of Massachussetts Medical Center, 55 Lake Avenue North Worcester,
MA 01605, USA
Dumont, M.
Hopital d'Alma, Alma, Canada
Dyrks, T.
Department of Pathology, University of Western Australia, Nedlands, 6009,
Western Australia
Earl, N. L.
Department of Medicine, Division of Neurology , Duke University Medical Center,
Durham, NC 27710, USA