Chasing genes in Alzheimer's and Parkinson's disease

153 Pages·2006·4.17 MB·English

by  Bertoli Avella

Chasing genes in
Alzheimer’s and Parkinson’s disease
Aida María Bertolí Avella
Cover: detail from painting by Sir Samuel LukeFildes, “The Doctor” ©Tate, London 2004
©Aida María Bertolí Avella,2004
No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means,
without permission of the author. Copyright of the published papers remains with the publishers.
ISBN: 90-77595-34-1
The work presented in this thesis was performed at the Department of Clinical Genetics and the Department of
Epidemiology & Biostatistics, Erasmus MC, Rotterdam, The Netherlands. Further fi nancial support was provided by
the Foundation Clinical Genetics, Rotterdam, The Netherlands.
The publication of this thesis was sponsored by the Alzheimer Nederland, Internationale Stichting Alzheimer
Onderzoek, Parkinson Patienten Vereniging, Roche Nederland BV and Eastman Chemical BV.
Layout and illustrations: Tom de Vries Lentsch
Photography: Ruud Koppenol, Tom de Vries Lentsch
Printed by: Optima Grafi sche Communicatie, Rotterdam
Chasing genes in
Alzheimer’s and Parkinson’s disease
Zoektocht naar genen betrokken bij de
ziekte van Alzheimer en de ziekte van Parkinson
Proefschrift
ter verkrijging van de graad van doctor
aan de Erasmus Universiteit Rotterdam
op gezag van de Rector Magnifi cus
Prof.dr. S.W.J. Lamberts
en volgens besluit van het College voor Promoties
De openbare verdediging zal plaatsvinden op
woensdag 9 juni 2004 om 11.45 uur
door
Aida María Bertolí Avella
geboren te Holguin, Cuba
Promotiecommissie
Promotoren: Prof.dr. B.A. Oostra
Prof.dr. C.M. van Duijn
Prof.dr. P. Heutink
Overige leden: Prof.dr. C. Wijmenga
Dr. J.C. van Swieten
Dr. E.J. Meijers-Heijboer

Contents
Chapter 1 Introduction 13
Alzheimer’s disease 14
Parkinson’s disease 24
Part 1
Chapter 2 A novel Presenilin1 mutation (L174M) in a large Cuban family with 51
early-onset Alzheimer’s disease
Chapter 3 Attitudes and knowledge about presymptomatic genetic testing 65
among individuals at high risk for familial, early-onset Alzheimer’s
disease
Part 2
Chapter 4 Suggestive linkage to chromosome 19 in a large Cuban family with 71
late-onset Parkinson’s disease
Chapter 5 Mapping genes involved in Parkinson’s disease susceptibility in a 87
genetically isolated population
Chapter 6 Novel parkin mutations detected in a large, multiethnic series of cases 101
with early-onset Parkinson’s disease
Chapter 7 General discussion 117
Summary 131
Samenvatting 133
Resumen 137
Acknowledgments 139
About the author 143
List of publications 147
Publications and manuscripts based on the studies described in this thesis
Chapter 1. Introduction
Chasing genes in Alzheimer’s disease and Parkinson’s disease.
A.M. Bertoli Avella, B. Oostra, P. Heutink. Human Genetics, 114(5):413-438, 2004.
Chapter 2.
A novel Presenilin1 mutation (L174M) in a large Cuban family with early-onset Alzheimer
disease.
A.M. Bertoli Avella, B. Marcheco Teruel, J.J. Llibre Rodriguez, N. Gomez Viera, I. Borrajero
Martinez, E.A. Severijnen, M. Joosse, C.M.van Duijn, L. Heredero Baute,
P. Heutink. Neurogenetics 4:97-104, 2002.
Chapter 3.
Attitudes and knowledge about presymptomatic genetic testing among individuals at high risk
for familial, early-onset Alzheimer’s disease.
B. Marcheco, A.M Bertoli, I. Rojas, and L. Heredero. Genetic Testing: 7(1):45-47, 2003.
Chapter 4.
Suggestive linkage to chromosome 19 in a large Cuban family with late-onset Parkinson’s
disease.
A.M. Bertoli Avella, J.L. Giroud-Benitez, V. Bonifati, E. Alvarez Gonzalez,
L. Heredero Baute, C.M. van Duijn, P. Heutink. Movement Disorders 18:1240-1249, 2003.
Chapter 5.
Mapping genes involved in Parkinson’s disease susceptibility in a genetically isolated
population.
Chapter 6.
Novel parkin mutations detected in a large, multiethnic series of cases with early-onset
Parkinson’s disease.
A.M. Bertoli Avella, J.L. Giroud Benitez, H. Ulucan, E. Barbosa,O. Schaap, H.C. van
der Linde, E. Martignoni, L. Lopiano, P. Lamberti, E. Fincati, A. Antonini, F. Stocchi, P.
Montagna, F. Squitieri, P. Marini, G. Abbruzzese, G. Fabbrini, R. Marconi, A. Dalla Libera,
G. Trianni, M. Guidi, De Gaetano, G. Boff Maegawa, N. De Leo, V. Gallai, G. de Rosa, N.
Vanacore, G. Meco,C.M. van Duijn, B. A. Oostra, P. Heutink, V. Bonifati, and The Italian
Parkinson Genetics Network *. Submitted to Movement Disorders, 2004.
Chapter 7. General Discussion