alzheimers disease

Alzheimer’s Disease ADVANCES IN ETIOLOGY, PATHOGENESIS AND THERAPEUTICS Alzheimer’s Disease: Advances in Etiology, Pathogenesis and Therapeutics Edited by Khalid Iqbal, Sangram S. Sisodia and Bengt Winblad Copyright & 2001 John Wiley & Sons Ltd Print ISBN 0-471-52176-0 Online ISBN 0-470-84645-3 This publication was supported by an educational grant from Janssen Pharmaceutica and Janssen Research Foundation Alzheimer’s Disease: Advances in Etiology, Pathogenesis and Therapeutics Edited by Khalid Iqbal, Sangram S. Sisodia and Bengt Winblad Copyright & 2001 John Wiley & Sons Ltd Print ISBN 0-471-52176-0 Online ISBN 0-470-84645-3 Alzheimer’s Disease ADVANCES IN ETIOLOGY, PATHOGENESIS AND THERAPEUTICS Edited by KHALID IQBAL New York State Institute for Basic Research, New York, USA SANGRAM S. SISODIA University of Chicago, Chicago, USA BENGT WINBLAD Karolinska Institute, Stockholm, Sweden JOHN WILEY & SONS, LTD Chichester . New York . Weinheim . Brisbane . Singapore . Toronto Alzheimer’s Disease: Advances in Etiology, Pathogenesis and Therapeutics Edited by Khalid Iqbal, Sangram S. Sisodia and Bengt Winblad Copyright & 2001 John Wiley & Sons Ltd Print ISBN 0-471-52176-0 Online ISBN 0-470-84645-3 Copyright & 2001 John Wiley & Sons Ltd. Baffins Lane, Chichester, West Sussex PO19 1UD, England National 01243 779777 International (+44) 1243 779777 e-mail (for orders and customer service enquiries): cs-books@wiley.co.uk Visit our Home Page on http://www.wiley.co.uk or http://www.wiley.com All Rights Reserved. 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Sisodia, Bengt Winblad p. ; cm. Includes bibliographical references and index. ISBN 0-471-52176-0 (cased : alk. paper) 1. Alzheimer’s disease—Congresses. I. Iqbal, Khalid. II. Sisodia, Sangram S. III. Winblad, Bengt. IV. International Conference on Alzheimer’s Diseases and Related Disorders (7th : 2000 : Washington, D.C.) [DNLM: 1. Alzheimer Disease—etiology—Congresses. 2. Alzheimer Disease— pathology—Congresses. 3. Alzheimer Disease—therapy—Congresses. WT 155 A4757 2001] RC523 A3753 2001 616.8’31—dc21 00–067218 British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 0-471-52176-0 Typeset from authors’ disks in 10 on 12 point Plantin by Dobbie Typesetting Limited, Tavistock, Devon Printed and bound in Great Britain by Biddles Ltd, Guildford and King’s Lynn This book is printed on acid-free paper responsibly manufactured from sustainable forestry, in which at least two trees are planted for each one used for paper production. Alzheimer’s Disease: Advances in Etiology, Pathogenesis and Therapeutics Edited by Khalid Iqbal, Sangram S. Sisodia and Bengt Winblad Copyright & 2001 John Wiley & Sons Ltd Print ISBN 0-471-52176-0 Online ISBN 0-470-84645-3 Contents List of Contributors xii Dedications xxvi Scientists Honored for Pioneering Research xxix Preface xxxv Acknowledgments xxxvi I. EPIDEMIOLOGY AND RISK FACTORS 1 1. The Transition from Normal Functioning to Dementia in the Aging Population Laura Fratiglioni, Brent Small, Bengt Winblad and Lars Ba ¨ ckman 3 2. Epidemiology of Alzheimer’s Disease and Dementia: Advances and Challenges Robert Katzman 11 3. Epidemiology of Dementia in Down’s Syndrome Nicole Schupf 23 II. GENETICS 31 4. A Genomic Search for Alzheimer’s Disease Genes Jonathan L. Haines, L. Renee Bailey, Janet M. Grubber, Dale Hedges, Jenifer L. Hall, Sandra West, Leonard Santoro, Beth Kemmerer, Anne M. Saunders, Allen D. Roses, Gary W. Small, William K. Scott, P. Michael Conneally, Jeffery M. Vance and Margaret A. Pericak-Vance 33 5. Candidate Genes Showing No Evidence of Association with Alzheimer’s Disease: Results of the NIMH-AD Genetics Initiative Lars Bertram, Deborah Blacker, Adam S. Crystal, Jennifer Jones, Devon Keeney, Laura A. MacKenzie-Ingano, Kristina Mullin, Sanjay Basu, Stephen Yhu, Melvin McInnis, Rodney C. P. Go, Aleister J. Saunders and Rudolph E. Tanzi 45 6. Familial Alzheimer’s Disease with Spastic Paraparesis Associated with a Mutation at Codon 261 of the Presenilin 1 Gene Martin R. Farlow, Jill R. Murrell, Frederick W. Unverzagt, Michael Phillips, Masaki Takao, Christine Hulette and Bernardino Ghetti 53 7. Genetic Analysis of the Presenilin Pathway in Drosophila Izhar Livne-Bar and Gabrielle L. Boulianne 61 8. Molecular Genetics and Transgenic Modeling of the Tauopathies Jada Lewis, Matt Baker, Marjon Van Slegtenhorst and Mike Hutton 71 9. Regulation of Four-repeat tau Expression: Interactions between Exon and Intron Splicing Regulatory Sequences Ian D’Souza and Gerard D. Schellenberg 87 Alzheimer’s Disease: Advances in Etiology, Pathogenesis and Therapeutics Edited by Khalid Iqbal, Sangram S. Sisodia and Bengt Winblad Copyright & 2001 John Wiley & Sons Ltd Print ISBN 0-471-52176-0 Online ISBN 0-470-84645-3 III. DIAGNOSIS AND CLINICAL COURSE 97 10. Preclinical Prediction of AD: Relation Between Neuropsychological and Neuroimaging Findings Marilyn S. Albert, Ronald J. Killiany, Keith Johnson, Rudolph E. Tanzi and Kenneth Jones 99 11. Neuropsychological Detection of Preclinical Alzheimer’s Disease: Results of a Neuropathological Series of ‘Normal’ Controls Kathleen A. Welsh-Bohmer, Christine Hulette, Donald Schmechel, James Burke and Ann Saunders 111 12. Potentially Reversible Conditions in Memory Clinic Patients Anne-Mette Hejl, Peter Høgh and Gunhild Waldemar 123 13. The Alzheimer’s Disease Centers’ Neuropsychological Database Initiative: A Resource for Alzheimer’s Disease Prevention Trials Michael Grundman, Hyun T. Kim, David Salmon, Martha Storandt, Glenn Smith, Steven Ferris, Richard Mohs, Jason Brandt, Rachelle Doody, Kathleen Welsh-Bohmer, Judith Saxton, Kathy Saine, Frederick Schmitt, Paula Ogrocki, Nancy Johnson, Diane Howieson, Michelle Papka, Joanne Green, Anthony Gamst, Walter Kukull and Leon J. Thal, for the Alzheimer’s Disease Centers’ Neuropsychological Database Initiative 129 14. Mild Cognitive Impairment: Transition from Aging to Alzheimer’s Disease Ronald C. Petersen 141 15. Brain Functional Imaging in Early and Preclinical Alzheimer’s Disease Agneta Nordberg, Vesna Jelic, Eva Arna ´ iz, Bengt La ˚ ngstro ¨ m and Ove Almkvist 153 16. Amyloid, PHF-tau, Ubiquitin and Synaptic Markers in the Progression of Alzheimer’s Disease: Immunochemical Analyses of Frontal Cortex from Prospectively Studied Elderly Humans D. S. Wang, E. Cochran, D. Bennett, E. Mufson, C. Eckman and D. W. Dickson 165 17. Imaging the Consequences of Alzheimer’s Disease Pathology Yaakov Stern and Scott Small 181 18. Influence of apoE Genotype and PET Brain Imaging on Preclinical Prediction of Alzheimer’s Disease Gary W. Small, Linda M. Ercoli, Daniel H.S. Silverman, S C. Huang, Susan Y. Bookheimer, Helen Lavretsky, Karen Miller, Prabha Siddarth, John C. Mazziotta, Ann M. Saunders, Margaret A. Pericak-Vance, Allen D. Roses, Jorge R. Barrio and Michael E. Phelps 193 19. Overview of Vascular Dementia William R. Markesbery 205 20. Clinical and Imaging Characteristics of Vascular Dementia in a Memory Clinic F. Pasquier, X. Douay, C. Delmaire, F. Lebert and J. P. Pruvo 219 21. MRI of Entorhinal Cortex and Hippocampus in Alzheimer’s Disease, Subcortical Ischemic Vascular Dementia and Mixed Dementia N. Schuff, A. T. Du, D. Amend, Y. Y. Hsu, M. P. Laakso, W. Jagust, H. C. Chui and M. W. Weiner 229 vi CONTENTS 22. Olfactory Function and Event-related Potentials in Alzheimer’s Disease Claire Murphy and Charlie D. Morgan 237 23. Phenotypic Differences in Cholinergic Markers within the Nucleus Basalis in Individuals with Mild Cognitive Impairment Elliott J. Mufson, Michele Gilmor, Shuang Y. Ma, Alan I. Levey and Jeffrey H. Kordower 253 24. Evaluating CNS Biomarkers for Alzheimer’s Disease John H. Growdon 265 25. CSF Markers for Early Alzheimer’s Disease Kaj Blennow, Pia Davidsson and Eugeen Vanmechelen 275 26. CSF-Phospho-tau (181P) as a Promising Marker for Discriminating Alzheimer’s Disease from Dementia with Lewy Bodies E. Vanmechelen, E. Van Kerschaver, K. Blennow, P. P. De Deyn, D. Galasko, L. Parnetti, C. J. M. Sindic, H. Arai, M. Riemenschneider, H. Hampel, H. Pottel, A. Valgaeren, F. Hulstaert and H. Vanderstichele 285 27. Increased Levels of a Minor Glycoform of Acetylcholinesterase in Alzheimer’s Disease Brain and Cerebrospinal Fluid Javier Sa ´ ez-Valero, Su San Mok, Lisa Fodero, Alberto Marcos, Maria-Sagrario Barquero, Catriona McLean and David H. Small 293 28. Plasma b-Amyloid as a Surrogate Genetic Marker in Late-onset Alzheimer’s Disease Nilufer Ertekin Taner, Neill Graff-Radford, Linda H. Younkin, Christopher Eckman, Jennifer Adamson, Daniel J. Schaid, John Blangero, Michael Hutton and Steven G. Younkin 303 29. Levels of Total and Deposited Ab are Correlated with Dementia S. Parvathy, J. Naslund, V. Haroutunian and J. D. Buxbaum 311 30. What Should We Tell Patients Attending a Memory Disorders Clinic About Their Diagnosis? Conor P. Maguire and Rebecca M. Slinn 319 IV. MECHANISMS OF NEURODEGENERATION 329 31. Innate Immunity, Autotoxicity and Degenerative Neurologies Patrick L. McGeer, Koju Yasojima and Edith G. McGeer 331 32. Neuroinflammatory Responses in the Alzheimer’s Disease Brain Promote the Oxidative Post-translational Modification of Amyloid Deposits Craig S. Atwood, Xudong Huang, Robert D. Moir, Mark A. Smith, Rudolph E. Tanzi, Alex E. Roher, Ashley I. Bush and George Perry 341 33. Plasma Antioxidants and Oxidative DNA Damage in Lymphocytes from Normal Aged People and Alzheimer’s Disease Patients Patrizia Mecocci, Maria Cristina Polidori, Tiziana Ingegni, Paola Mattioli, Antonio Cherubini, Marco Catani, Roberta Cecchetti and Umberto Senin 363 34. Oxidative Damage and Antioxidant Responses in Alzheimer’s Disease George Perry, Akihiko Nunomura, Jesus Avila, Mar Perez, Catherine A. Rottkamp, Craig S. Atwood, Xiongwei Zhu, Gjumrakch Aliev, Adam D. Cash and Mark A. Smith 371 CONTENTS vii 35. Cyclooxygenase (COX)-2 and Clinical Progression of Alzheimer’s Disease Dementia: Implications in the Role of Neuronal COX-2 in Cell Cycle Giulio Maria Pasinetti 379 36. Parallels between the Redox Properties and Toxicity of Ab in Alzheimer’s Disease and Mutant Cu/Zn-SOD in Familial Amyotrophic Lateral Sclerosis Ashley I. Bush 393 37. b-Amyloid Toxicity: Diverse Biological Activities Drive Multiple Cellular Mechanisms C. W. Cotman, L. Tong, A. Anderson, D. Cribbs and J. Su 407 38. Mechanisms of Ab Production and Ab Degradation: Routes to the Treatment of Alzheimer’s Disease D. J. Selkoe, W. Xia, W. T. Kimberly, K. Vekrellis, D. Walsh, W. P. Esler and M. S. Wolfe 421 39. A High Fat, High Cholesterol Diet Accelerates b-Amyloid Accumulation in the CNS of a Transgenic Mouse Model of Alzheimer’s Disease Lorenzo M. Refolo, Brian Malester, John LaFrancois, Tara Bryant-Thomas, Rong Wang, G. Stephen Tint, Kumar Sambamurti, Karen Duff and Miguel A. Pappolla 433 40. Electron Microscopy and X-ray Diffraction Studies further Confirm the Efficacy of PTI-00703TM 1 (Cat’s Claw Derivative) as a Potential Inhibitor of Alzheimer’s b-Amyloid Protein Fibrillogenesis Gerardo M. Castillo, Daniel A. Kirschner, Ann G. Yee and Alan D. Snow 449 41. Accelerated Ab Generation in a Cell Model of Alzheimer’s Disease-related Endosomal–Lysosomal System Upregulation Paul M. Mathews, Carolyn B. Guerra, Ying Jiang, Benjamin H. Kao, Ravi Dinakar, Pankaj Mehta, Anne M. Cataldo and Ralph A. Nixon 461 42. The Amyloid Precursor Protein V717I Mutation Increases Susceptibility to Cell Death in a Cholesterol-dependent Manner Luigi Puglielli, Laura A. MacKenzie Ingano, Rudolph E. Tanzi and Dora M. Kovacs 469 43. Intracellular and Secreted Ab 42/40 Ratios Are Differently Influenced by APP Mutations Heike S. Grimm, Stefan F. Lichtenthaler, Konrad Beyreuther and Tobias Hartmann 479 44. Familial British Dementia Jorge Ghiso, Tamas Re ´ ve ´ sz, Agueda Rostagno, Ruben Vidal, Gordon Plant and Blas Frangione 487 45. Cellular Metabolism of Familial British Dementia-associated BRI-L Seong-Hun Kim and Sangram S. Sisodia 495 46. A Decamer Duplication in the BRI Gene Originates a de novo Amyloid Peptide that Causes Dementia in a Danish Kindred Ruben G. Vidal, Tamas Re ´ ve ´ sz, Agueda Rostagno, Toke Bek, Hans Braendgaard, Gordon Plant, Jorge Ghiso and Blas Frangione 507 47. Familial Alzheimer’s Disease-linked Mutant Presenilins Attenuate Capacitative Calcium Entry Isaac Cheng, Andrew S. Yoo, Rudolph E. Tanzi and Tae-Wan Kim 515 viii CONTENTS 48. Presenilin-1 Is a Regulatory Component of the Cadherin Cell Adhesion Complex: Implications for Alzheimer’s Disease Anastasio Georgakopoulos, Philippe Marambaud, Nikolaos K. Robakis and Lia Baki 521 49. Presenilins and Notch Signaling Pathway Weihong Song and Bruce A. Yankner 531 50. Functional Consequences of the Association of PS1 with b-Catenin Salvador Soriano, David E. Kang, Nathalie Chevallier, Hui Zheng and Edward H. Koo 541 51. A Novel Protease Active Site Motif Conserved in Presenilins and Polytopic Bacterial Aspartyl Proteases? Harald Steiner and Christian Haass 549 52. The Unfolded Protein Response-mediated Upregulation of BiP and CHOP Is not Affected by Presenilin Expression Naoyuki Sato and Gopal Thinakaran 559 53. Mechanisms of a-Synuclein and NAC Fibrillogenesis Makoto Hashimoto, Edward Rockenstein, Takato Takenouchi, Margaret Mallory and Eliezer Masliah 569 54. Neurofibrillary Degeneration: Patterns of Tau Isoform Expression Andre ´ Delacourte 587 55. Phosphorylation, Microtubule Binding and Aggregation of Tau Protein in Alzheimer’s Disease Jesu ´ sA ´ vila, Jose ´ J. Lucas, Filip Lim, Mar Pe ´ rez, Fe ´ lix Herna ´ ndez, Montserrat Arrasate, Rosario Armas Portela, Elsa Champion, George Perry, Mark A. Smith and Javier Dı ´ az Nido 601 56. Phosphorylation of Protein Tau and Rescue of Protein Tau-induced Axonopathy by GSK-3b in GSK-3b6htau40 Double Transgenic Mice Kurt Spittaels, Chris Van den Haute, Jo Van Dorpe, Hugo Geerts and Fred Van Leuven 609 57. Pathogenic Implication of Altered Tau Properties Caused by FTDP-17 Mutations P. Nacharaju, S. Yen, M. DeTure, C. Easson, M. Hutton and S H. Yen 621 58. A Hexapeptide Motif ( 306 VQIVYK 311 )-forming b Structure Induces the Aggregation of Tau Protein to Paired Helical Filaments M. von Bergen, J. Biernat, E M. Mandelkow and Eckhard Mandelkow 631 V. ANIMAL AND CELLULAR MODELS 641 59. Formation of Neurofibrillary Tangles in Mouse Brain Akihiko Takashima and Kentaro Tanemura 643 60. Inducible Transgenic Expression of Wild-type tau in H4 Neuroglioma Cells Michael DeTure, Li-Wen Ko, Colin Easson, Mike Hutton and Shu-Hui Yen 651 61. Lewy-like Pathology in Mice Transgenic for Mutant (A53T) and Wild-type Human a-Synuclein Bernd Sommer, Samuel Barbieri, Katja Hofele, Karl-Heinz Wiederhold, Alphonse Probst, Claudia Mistl, Simone Danner, Sabine Kauffmann, Willibrordus Spooren, Markus Tolnay, Graeme Bilbe and Herman van der Putten 661 CONTENTS ix 62. Somal and Neuritic Accumulation of the Parkinson’s Disease-associated Mutant [A30P]a-Synuclein in Transgenic Mice Phillipp J. Kahle, Manuela Neumann, Laurence Ozmen, Hans A. Kretzschmar and Christian Haass 671 63. Ex vivo Transmission of Mouse-adapted Prion Strains to N2a and GT1-7 Cell Lines Sylvain Lehmann, Hubert Laude, David A. Harris, Richard I. Carp, Didier Vilette, Shigeru Katamine, Jean-Yves Madec and Noriyuki Nishida 679 64. In Vivo Perturbation of Lysosomal Function Promotes Neurodegeneration in the PS1 M146V /APP K670N,M671L Mouse Model of Alzheimer’s Disease Pathology Ralph A. Nixon, Paul M. Mathews, Anne M. Cataldo, Panaiyur S. Mohan, Stephen D. Schmidt, Karen Duff, Martin Berg, Neville Marks, Corinne Peterhoff and Henry Sershen 687 65. Changes in Cognitive Characteristics of Tg(APP)CRND8 Mice at Early Stages of Immunization with Beta-Amyloid Peptide Christopher Janus, Jacqueline Pearson, Patrick Horne, Richard Renlund, Karen Parisien, Azhar Chishti, Donna Heslin, Catherine Bergeron, Paul Fraser, Peter St George-Hyslop and David Westaway 697 VI. THERAPEUTICS AND THERAPEUTIC STRATEGIES 705 66. Galantamine, a Novel Treatment for Alzheimer’s Disease: A Review of Long-term Benefits to Patients and Caregivers Pierre Tariot and Bengt Winblad 707 67. Benefits of Donepezil on Cognition, Function and Neuropsychiatric Symptoms in Patients with Mild and Moderate Alzheimer’s Disease over One Year Gunhild Waldemar, Bengt Winblad, Knut Engedal, Hilkke Soininen, Frans Verhey, Anders Wimo, Anne-Lena Wetterholm, Richard Zhang, Anders Haglund, Ponni Subbiah and the Donepezil Nordic Study Group 725 68. Characterization of Alzheimer’s b-Secretase Protein BACE: Processing and Other Post-translational Modifications Mitsuru Haniu, Brian D. Bennett, Paul Denis, Yunjen Young, Elizabeth A. Mendiaz, Janis Fuller, John O. Hui, Steven Kahn, Safura Babu-Khan, Sandra Ross, Teresa Burgess, Viswanatham Katta, Margery Nicolson, Jonathan Lull, Shue-Yuan Wang, Gary Rogers, Robert Vassar and Martin Citron 739 69. Androgen Treatment Reduces Cognitive Deficits in Female apoE4 Transgenic Mice Jacob Raber, Anthony LeFevour and Lennart Mucke 70. Studies with the Memory-enhancing Drug AIT-082 in PC12 Cells Debomoy K. Lahiri, Yuan-Wen Ge and Martin R. Farlow 747 71. Generation of Auto-antibodies toward Alzheimer’s Disease Vaccination Beka Solomon and Dan Frenkel 759 72. Toward the Identification of c-Secretase: Using Transition State Analog Inhibitors William P. Esler, W. Taylor Kimberly, Beth L. Ostaszewski, Weiming Xia, Dennis J. Selkoe and Michael S. Wolfe 777 x CONTENTS [...]... Alzheimer’s Disease and Related Disorders Eva was one of the most meticulous and outstanding scientists, but at the same time a reserved and quiet person Her death is a truly great loss to the Alzheimer’s disease field and we miss her HENRY M WISNIEWSKI, ‘PIONEER AND VISIBLE’ Henry M Wisniewski, a pioneer and one of the most visible Alzheimer’s disease researchers, died of chronic kidney disease on 5... or co-edited several books on Alzheimer’s disease and related disorders With Henry’s death, neuroscience, especially the Alzheimer’s disease research community, has lost a pioneer and a provocative discussant of Alzheimer’s disease research He is survived by his wife, Krystyna Wisniewski, and his son, Thomas Wisniewski Khalid Iqbal Bengt Winblad Alzheimer’s Disease: Advances in Etiology, Pathogenesis... important research findings have been made on the biology, diagnosis and treatment of the disease since the publication of our previous book on Alzheimer’s disease, 2 years ago In the present book the scientists studying the disease have described the advances made by them and others in epidemiology and genetic risk factors, disease mechanisms, early diagnosis and in therapeutic opportunities and new therapeutic... Alzheimer’s disease At the Institute, along with Jerzy Wegiel, he carried out pioneering studies on the role of microglia in senile plaque formation in Alzheimer’s disease; and with Eirene Popovitch, Andrzej Vorbrodt and Richard Carp, he demonstrated the occurrence of Alzheimer’s-type plaques and tangles in conditions with developmental disabilities, and the distribution of plaques in prion disease and... histopathology of Alzheimer’s disease and related disorders They successfully employed these techniques, not only to correlate distinctive pigmentation patterns of several types of nerve cells with the features of these cells in Golgi and immunostained sections but also, in 1989, to identify a new, not infrequently occurring tauopathy, argyrophilic grain disease or ‘Braak’s disease , which is often marked... Disease Research Center grant, also from the National Institute on Aging Dr Berg became a full Professor in the Department of Neurology in 1989, leaving private practice to focus full-time on dementia research until he retired in 1998 He and his colleagues developed the Clinical Dementia Rating (CDR) which is now used worldwide to stage Alzheimer’s disease and distinguish between mild Alzheimer’s disease. .. Alzheimer’s disease was abnormally hyperphosphorylated The abnormal hyperphosphorylation of tau is not only one of the most important findings made in the Alzheimer’s disease field but also opened a major new area of research Subsequent studies by Dr Grundke-Iqbal and her colleagues demonstrated that the levels of tau in abnormally hyperphosphorylated form are increased several-fold in Alzheimer’s disease, ... Alzheimer’s Disease Research in 1992 A recent contribution, together with Dr Karen Bick, is the oral history, Alzheimer Disease: The Changing View, a book describing the events between 1960 and 1980 that led to recognition of the public health importance of AD GEORGE M MARTIN George M Martin is Professor of Pathology, Adjunct Professor of Genetics and Associate Director of the Alzheimer’s Disease Research... 0-471-52176-0 Online ISBN 0-470-84645-3 Preface Alzheimer’s disease has no geographical, racial or economic boundaries It is the major cause of dementia in middle- to old-age individuals throughout the world With the increase in human life span, the prevalence of this ageassociated disease continues to grow The importance and the scientific challenge of this disease have been well recognized by the neuroscience... persons and patients with Alzheimer’s disease In 1974, Henry left Einstein to take over the position of Director, MRC Demyelinating Diseases Unit, in Newcastle upon Tyne, UK In collaboration xxviii DEDICATIONS with Harish Narang at the MRC Unit Henry confirmed the ultrastructure of paired helical filaments by tilt stage microcopy of these filaments in Alzheimer’s disease brain and X-ray images of the . (7th : 2000 : Washington, D.C.) [DNLM: 1. Alzheimer Disease etiology—Congresses. 2. Alzheimer Disease pathology—Congresses. 3. Alzheimer Disease therapy—Congresses. WT 155 A4757 2001] RC523. (cased : alk. paper) 1. Alzheimer’s disease Congresses. I. Iqbal, Khalid. II. Sisodia, Sangram S. III. Winblad, Bengt. IV. International Conference on Alzheimer’s Diseases and Related Disorders (7th. Alzheimer’s Disease ADVANCES IN ETIOLOGY, PATHOGENESIS AND THERAPEUTICS Alzheimer’s Disease: Advances in Etiology, Pathogenesis and Therapeutics Edited