P. Riederer, D. B. CaIne, R. Horowski, Y. Mizuno, W. Poewe, M. B. H. Youdim (eds.) Advances in Research on N eurodegeneration.

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2 P. Riederer, D. B. CaIne, R. Horowski, Y. Mizuno, W. Poewe, M. B. H. Youdim (eds.) Advances in Research on N eurodegeneration Volume 5 Springer WienN ewyork

3 Prof. Dr. P. Riederer Department of Psychiatry, University of Wiirzburg, Federal Republic of Germany Prof. Dr. D. B. CaIne Neurodegenerative Disorders Centre, University of British Columbia, Vancouver, Canada Dr. R. Horowski Clinical Research, Schering AG, Berlin, Federal Republic of Germany Prof. Dr. Y. Mizuno Department of Neurology, Juntendo University, Tokyo, Japan Prof. Dr. W. Poewe Department of Neurology, University of Innsbruck, Austria Prof. Dr. M. B. H. You dim Institute of Pharmacology, Technion - Israel Institute of Technology, Faculty of Medicine, Haifa, Israel This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machines or similar means, and storage in data banks Springer-Verlag Wien Softcover reprint of the hardcover 1 st edition 1997 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 accuracy by consulting other pharmaceutical literature. The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Printing: A. Holzhausens Nfg., A-I070 Wien Graphic design: Ecke Bonk Printed on acid-free and chlorine-free bleached paper With 45 Figures ISBN-13: DOl: / e-isbn-13:

4 Preface Volume 5 of the series "Advances in Research on Neurodegeneration" is concerned with themes which are currently the focus of intensive research, and in which advances in our understanding of the pathological mechanisms underlying neurodegenerative diseases are expected in the near future. The first section contains five reviews devoted to the various neuroimaging technologies. The discussion is concerned with the question of whether neuroimaging techniques make it possible to follow the process of degeneration as it occurs, and which methods offer the required sensitivity and quantifiability for this purpose. However, the question needs to be examined of whether, given the physical and chemical limitations of these techniques, even under optimal conditions, anatomical resolution can be improved to the extent that neurodegenerative diseases can be diagnosed earlier than currently possible and a confident diagnosis made. The possibilities of using neuroimaging techniques to provide information regarding the effects of neuroprotective or neuroregenerative therapeutic strategies, and for correlating the results of neuropsychological research with imaging data are also discussed. The second section is concerned with the significance of endogenous or exogenous neurotoxins as triggers for neurodegenerative processes that may lead to Parkinsonism. Vulnerability factors, which include such factors as nerve ending sensitivity, the synergistic effects of drugs and the various mechanisms underlying different toxins are discussed. A further important chapter considers the question of cell death; that is, programmed cell death, apoptosis and necrosis, and their respective mechanisms. Questions regarding terminology, as well as molecular biological and genetic mechanisms, are the main points of interest. The validation and limitations of neuropathological research methods, as well as possible therapeutic consequences are also discussed. The fourth chapter is concerned with new developments in the area of immunoinflammatory mechanisms and infectious diseases which may trigger neurological diseases. Both basic experimental studies and clinically oriented research are reviewed. The focus is on multiple sclerosis and prion diseases. The rapid publication of this volume provides the reader with an up-to-date overview of these themes in a-compact form. The publication of the Proceedings of the Fifth International Winter Conference on Neurodegeneration (Spitzingsee, Bavaria, February 1996) was

5 VI Preface made possible by the generous assistance of Schering AG, Berlin, and Lilly, Bad Homburg, Germany. We thank Springer-Verlag Wien New York for their usual excellent quality and swiftness. Wtirzburg, December 1996 P. Riederer

6 Contents Brain imaging revisited Laubenberger, J.: Magnetic Resonance: A multimodal approach to the brain? 3 Brucke, T., Asenbaum, S., Pirker, W., Djamshidian, S., Wenger, S., Wober, Ch., Muller, Ch., Podreka, I.: Measurement of the dopaminergic degeneration in Parkinson's disease with [123I]~-CIT and SPECT Bissessur, S., Tissingh, G., Wolters, E. Ch., Scheltens, Ph.: rcbf SPECT in Parkinson's disease patients with mental dysfunction Tissingh, G., Booij, J., Winogrodzka, A., van Royen, E. A., Wolters, E. Ch.: IBZM - and ~-CIT -SPECT of the dopaminergic system in parkinsonism Leenders, K. L.: Pathophysiology of movement disorders studied using PET CaIne, D. B., de la Fuente-Fermindez, R., Kishore, A.: Contributions of Positron Emission Tomography to elucidating the pathogenesis of Idiopathic Parkinsonism and Dopa Responsive Dystonia Endogenous and exogenous neurotoxins Glinka, Y., Gassen, M., Youdim, M. B. H.: Mechanism of 6-Hydroxydopamine neurotoxicity Shirvan, A., Ziv, I., Barzilai, A., Djaldeti, R., Zilkh-Falb, R., Michlin, T., Melamed, E.: Induction of mitosis-related genes during dopamine-triggered apoptosis in sympathetic neurons Hirsch, E. C., Faucheux, B., Damier, P., Mouatt-Prigent, A., Agid, Y.: Neuronal vulnerability in Parkinson's disease Naoi, M., Maruyama, W., Dostert, P., Hashizume, Y.: N-Methyl-(R)salsolinol as a dopaminergic neurotoxin: From an animal model to an early marker of Parkinson's disease Heim, Ch., Sontag, K.-H.: The halogenated tetrahydro-~-carboline "TaClo": A progressively-acting neurotoxin Programmed cell death, apoptosis, necrosis and in between Weller, M., Schulz, J. B., Wullner, U., Loschmann, P. A., Klockgether, T., Dichgans, J.: Developmental abd genetic regulation of programmed neuronal death..... ', Mochizuki, H., Mori, H., Mizuno, Y.: Apoptosis in neurodegenerative disorders.. 125

7 VIII Contents Bancher, C., Lassmann, H., Breitschopf, H., Jellinger, K.: Mechanisms of cell death in Alzheimer's disease O'Byrne, M., Tipton, K., McBean, G., Kollegger, H.: Assessment of neurotoxicity and "neuroprotection"., Immunoinflammatory mechanisms, infective diseases causing neurological disorders Sadovnick, A. D.: Update on management and genetics of multiple sclerosis 167 Hartung, H.-P., Rieckmann, P.: Pathogenesis of immune-mediated demyelination in the CNS Lassmann, H.: Basic mechanisms of brain inflammation Kretzschmar, H. A., Giese, A., Brown, D. R., Herms, J., Keller, B., Schmidt, B., Groschup, M.: Cell death in prion disease Subject Index Listed in Current Contents / Life Sciences