Alzheimer's Disease: Advances in Etiology, Pathogenesis and Therapeutics

Copyright © 2001 John Wiley & Sons, Ltd

Alzheimer's Disease: Advances in Etiology, Pathogenesis and Therapeutics

Editor(s): Khalid Iqbal, Sangram S. Sisodia, Bengt Winblad

Published Online: 18 APR 2002

Print ISBN: 9780471521761

Online ISBN: 9780470846452

DOI: 10.1002/0470846453

About this Book

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About The Product

Alzheimer's Disease is an ever present problem affecting millions of people around the world and, as people's average lifespan lengthens, its prevalence is set to increase. A global effort is needed to combat the disease, including research to investigate the causes, development of effective treatments and, ultimately, prevention of the disease. Published every two years, these timely books discuss the very latest research.

This new volume provides a unique source of reference to the important work being done in this field, it gives academics and clinicians an opportunity to learn about cutting edge developments and covers all aspects of Alzheimer's Disease, including diagnosis, clinical course, epidemiological course and therapeutics and disease mechanisms.

Alzheimer's Disease: Advances in Etiology, Pathogenesis and Therapeutics will provide essential information for basic and clinical researchers in Alzheimer's Disease and other dementias as well as for those who care for patients.

Table of contents

    1. You have free access to this content
      Front Matter and Index (pages i–xxxvi)

    1. You have free access to this content
      Colour Plates (pages c1–c4)

  3. Part I: Epidemiology and Risk Factors

    1. Chapter 1

      The Transition from Normal Functioning to Dementia in the Aging Population (pages 1–10)

      Laura Fratiglioni, Brent Small, Bengt Winblad and Lars Bäckman

    2. Chapter 2

      Epidemiology of Alzheimer's Disease and Dementia: Advances and Challenges (pages 11–21)

      Robert Katzman

    3. Chapter 3

      Epidemiology of Dementia in Down's Syndrome (pages 23–30)

      Nicole Schupf

  4. Part II: Genetics

    1. Chapter 4

      A Genomic Search for Alzheimer's Disease Genes (pages 31–43)

      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

    2. Chapter 5

      Candidate Genes Showing No Evidence of Association with Alzheimer's Disease: Results of the NIMH-AD Genetics Initiative (pages 45–51)

      Lars Bertram, Deborah Blacker, Adam S. Crystal, Jennifer Jones, Devon Keeney, Laura MacKenzie-Ingano, Kristina Mullin, Sanjay Basu, Stephen Yhu, Melvin McInnis, Rodney C. P. Go, Aleister J. Saunders and Rudolph E. Tanzi

    3. Chapter 6

      Familial Alzheimer's Disease with Spastic Paraparesis Associated with a Mutation at Codon 261 of the Presenilin 1 Gene (pages 53–60)

      Martin R. Farlow, Jill R. Murrell, Frederick W. Unverzagt, Michael Phillips, Masaki Takao, Christine Hulette and Bernardino Ghetti

    4. Chapter 7

      Genetic Analysis of the Presenilin Pathway in Drosophila (pages 61–70)

      Izhar Livne-Bar and Gabrielle L. Boulianne

    5. Chapter 8

      Molecular Genetics and Transgenic Modeling of the Tauopathies (pages 71–85)

      Jada Lewis, Matt Baker, Marjon Van Slegtenhorst and Mike Hutton

    6. Chapter 9

      Regulation of Four-Repeat tau Expression: Interactions between Exon and Intron Splicing Regulatory Sequences (pages 87–95)

      Ian D'Souza and Gerard D. Schellenberg

  5. Part III: Diagnosis and Clinical Course

    1. Chapter 10

      Preclinical Prediction of AD: Relation Between Neuropsychological and Neuroimaging Findings (pages 97–110)

      Marilyn S. Albert, Ronald J. Killiany, Keith Johnson, Rudolph E. Tanzi and Kenneth Jones

    2. Chapter 11

      Neuropsychological Detection of Preclinical Alzheimer's Disease: Results of a Neuropathological Series of ‘Normal’ Controls (pages 111–122)

      Kathleen A. Welsh-Bohmer, Christine Hulette, Donald Schmechel, James Burke and Ann Saunders

    3. Chapter 12

      Potentially Reversible Conditions in Memory Clinic Patients (pages 123–128)

      Anne-Mette Hejl, Peter Høgh and Gunhild Waldemar

    4. Chapter 13

      The Alzheimer's Disease Centers' Neuropsychological Database Initiative: A Resource for Alzheimer's Disease Prevention Trials (pages 129–140)

      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

    5. Chapter 14

      Mild Cognitive Impairment: Transition from Aging to Alzheimer's Disease (pages 141–151)

      Ronald C. Petersen

    6. Chapter 15

      Brain Functional Imaging in Early and Preclinical Alzheimer's Disease (pages 153–164)

      Agneta Nordberg, Vesna Jelic, Eva Arnáiz, Bengt Långström and Ove Almkvist

    7. Chapter 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 (pages 165–180)

      D. S. Wang, E. Cochran, D. Bennett, E. Mufson, C. Eckman and D. W. Dickson

    8. Chapter 17

      Imaging the Consequences of Alzheimer's Disease Pathology (pages 181–192)

      Yaakov Stern and Scott Small

    9. Chapter 18

      Influence of apoE Genotype and PET Brain Imaging on Preclinical Prediction of Alzheimer's Disease (pages 193–203)

      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

    10. Chapter 19

      Overview of Vascular Dementia (pages 205–218)

      William R. Markesbery

    11. Chapter 20

      Clinical and Imaging Characteristics of Vascular Dementia in a Memory Clinic (pages 219–228)

      F. Pasquier, X. Douay, C. Delmaire, F. Lebert and J.P. Pruvo

    12. Chapter 21

      MRI of Entorhinal Cortex and Hippocampus in Alzheimer's Disease, Subcortical Ischemic Vascular Dementia and Mixed Dementia (pages 229–236)

      N. Schuff, A. T. Du, D. Amend, Y. Y. Hsu, M. P. Laakso, W. Jagust, H. C. Chui and M. W. Weiner

    13. Chapter 22

      Olfactory Function and Event-Related Potentials in Alzheimer's Disease (pages 237–251)

      Claire Murphy and Charlie D. Morgan

    14. Chapter 23

      Phenotypic Differences In Cholinergic Markers Within The Nucleus Basalis In Individuals With Mild Cognitive Impairment (pages 253–264)

      Elliott J. Mufson, Michele Gilmor, Shuang Y. Ma, Alan I. Levey and Jeffrey H. Kordower

    15. Chapter 24

      Evaluating CNS Biomarkers for Alzheimer's Disease (pages 265–273)

      John H. Growdon

    16. Chapter 25

      CSF Markers for Early Alzheimer's Disease (pages 275–283)

      Kaj Blennow, Pia Davidsson and Eugeen Vanmechelen

    17. Chapter 26

      CSF-Phospho-tau (181P) as a Promising Marker for Discriminating Alzheimer's Disease from Dementia with Lewy Bodies (pages 285–291)

      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

    18. Chapter 27

      Increased Levels of a Minor Glycoform of Acetylcholinesterase in Alzheimer's Disease Brain and Cerebrospinal Fluid (pages 293–301)

      Javier Sáez-Valero, Su San Mok, Lisa Fodero, Alberto Marcos, Maria-Sagrario Barquero, Catriona McLean and David H. Small

    19. Chapter 28

      Plasma β-Amyloid as a Surrogate Genetic Marker in Late-Onset Alzheimer's Disease (pages 303–310)

      Nilufer Ertekin Taner, Neill Graff-Radford, Linda H. Younkin, Christopher Eckman, Jennifer Adamson, Daniel J. Schaid, John Blangero, Michael Hutton and Steven G. Younkin

    20. Chapter 29

      Levels of Total and Deposited Aβ are Correlated with Dementia (pages 311–317)

      S. Parvathy, J. Naslund, V. Haroutunian and J. D. Buxbaum

    21. Chapter 30

      What Should We Tell Patients Attending a Memory Disorders Clinic About Their Diagnosis? (pages 319–328)

      Conor P. Maguire and Rebecca M. Slinn

  6. Part IV: Mechanisms of Neurodegeneration

    1. Chapter 31

      Innate Immunity, Autotoxicity and Degenerative Neurologies (pages 329–339)

      Patrick L. McGeer, Koju Yasojima and Edith G. McGeer

    2. Chapter 32

      Neuroinflammatory Responses in the Alzheimer's Disease Brain Promote the Oxidative Post-translational Modification of Amyloid Deposits (pages 341–361)

      Craig S. Atwood, Xudong Huang, Robert D. Moir, Mark A. Smith, Rudolph E. Tanzi, Alex E. Roher, Ashley I. Bush and George Perry

    3. Chapter 33

      Plasma Antioxidants and Oxidative DNA Damage in Lymphocytes from Normal Aged People and Alzheimer's Disease Patients (pages 363–369)

      Patrizia Mecocci, Maria Cristina Polidori, Tiziana Ingegni, Paola Mattioli, Antonio Cherubini, Marco Catani, Roberta Cecchetti and Umberto Senin

    4. Chapter 34

      Oxidative Damage and Antioxidant Responses in Alzheimer's Disease (pages 371–378)

      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

    5. Chapter 35

      Cyclooxygenase (COX)-2 and Clinical Progression of Alzheimer's Disease Dementia: Implications in the Role of Neuronal COX-2 in Cell Cycle (pages 379–392)

      Giulio Maria Pasinetti

    6. Chapter 36

      Parallels between the Redox Properties and Toxicity of Aβ in Alzheimer's Disease and Mutant Cu/Zn-SOD in Familial Amyotrophic Lateral Sclerosis (pages 393–406)

      Ashley I. Bush

    7. Chapter 37

      β-Amyloid Toxicity: Diverse Biological Activities Drive Multiple Cellular Mechanisms (pages 407–420)

      C. W. Cotman, L. Tong, A. Anderson, D. Cribbs and J. Su

    8. Chapter 38

      Mechanisms of Aβ Production and Aβ Degradation: Routes to the Treatment of Alzheimer's Disease (pages 421–432)

      D. J. Selkoe, W. Xia, W. T. Kimberly, K. Vekrellis, D. Walsh, W. P. Esler and M. S. Wolfe

    9. Chapter 39

      A High Fat, High Cholesterol Diet Accelerates β-Amyloid Accumulation in the CNS of a Transgenic Mouse Model of Alzheimer's Disease (pages 433–447)

      Lorenzo M. Refolo, Brian Malester, John Lafrancois, Tara Bryant-Thomas, Rong Wang, G. Stephen Tint, Kumar Sambamurti, Karen Duff and Miguel A. Pappolla

    10. Chapter 40

      Electron Microscopy and X-ray Diffraction Studies further Confirm the Efficacy of PTI-00703® (Cat's Claw Derivative) as a Potential Inhibitor of Alzheimer's β-Amyloid Protein Fibrillogenesis (pages 449–460)

      Gerardo M. Castillo, Daniel A. Kirschner, Ann G. Yee and Alan D. Snow

    11. Chapter 41

      Accelerated Aβ Generation in a Cell Model of Alzheimer's Disease-related Endosomal–Lysosomal System Upregulation (pages 461–467)

      Paul M. Mathews, Carolyn B. Guerra, Ying Jiang, Benjamin H. Kao, Ravi Dinakar, Pankaj Mehta, Anne M. Cataldo and Ralph A. Nixon

    12. Chapter 42

      The Amyloid Precursor Protein V717I Mutation Increases Susceptibility to Cell Death in a Cholesterol-dependent Manner (pages 469–477)

      Luigi Puglielli, Laura A. Mackenzie Ingano, Rudolph E. Tanzi and Dora M. Kovacs

    13. Chapter 43

      Intracellular and Secreted Aβ42/40 Ratios Are Differently Influenced by APP Mutations (pages 479–486)

      Heike S. Grimm, Stefan F. Lichtenthaler, Konrad Beyreuther and Tobias Hartmann

    14. Chapter 44

      Familial British Dementia (pages 487–493)

      Jorge Ghiso, Tamas Révész, Agueda Rostagno, Ruben G. Vidal, Gordon Plant and Blas Frangione

    15. Chapter 45

      Cellular Metabolism of Familial British Dementia-associated BRI-L (pages 495–505)

      Seong-Hun Kim and Sangram S. Sisodia

    16. Chapter 46

      A Decamer Duplication in the BRI Gene Originates a de novo Amyloid Peptide that Causes Dementia in a Danish Kindred (pages 507–513)

      Ruben G. Vidal, Tamas Révész, Agueda Rostagno, Toke Bek, Hans Braendgaard, Gordon Plant, Jorge Ghiso and Blas Frangione

    17. Chapter 47

      Familial Alzheimer's Disease-linked Mutant Presenilins Attenuate Capacitative Calcium Entry (pages 515–519)

      Isaac Cheng, Andrew S. Yoo, Rudolph E. Tanzi and Tae-Wan Kim

    18. Chapter 48

      Presenilin-1 is a Regulatory Component of the Cadherin Cell Adhesion Complex: Implications for Alzheimer's Disease (pages 521–530)

      Anastasios Georgakopoulos, Philippe Marambaud, Nikolaos K. Robakis and Lia Baki

    19. Chapter 49

      Presenilins and Notch Signaling Pathway (pages 531–539)

      Weihong Song and Bruce A. Yankner

    20. Chapter 50

      Functional Consequences of the Association of PS1 with β-Catenin (pages 541–548)

      Salvador Soriano, David E. Kang, Nathalie Chevallier, Hui Zheng and Edward H. Koo

    21. Chapter 51

      A Novel Protease Active Site Motif Conserved in Presenilins and Polytopic Bacterial Aspartyl Proteases? (pages 549–558)

      Harald Steiner and Christian Haass

    22. Chapter 52

      The Unfolded Protein Response-mediated Upregulation of BiP and CHOP Is not Affected by Presenilin Expression (pages 559–567)

      Naoyuki Sato and Gopal Thinakaran

    23. Chapter 53

      Mechanisms of α-Synuclein and NAC Fibrillogenesis (pages 569–586)

      Makoto Hashimoto, Edward Rockenstein, Takato Takenouchi, Margaret Mallory and Eliezer Masliah

    24. Chapter 54

      Neurofibrillary Degeneration: Patterns of Tau Isoform Expression (pages 587–599)

      André Delacourte

    25. Chapter 55

      Phosphorylation, Microtubule Binding and Aggregation of Tau Protein in Alzheimer's Disease (pages 601–607)

      Jesús Ávila, José J. Lucas, Filip Lim, Mar Pérez, Félix Hernández, Montserrat Arrasate, Rosario Armas Portela, Elsa Champion, George Perry, Mark A. Smith and Javier Díaz Nido

    26. Chapter 56

      Phosphorylation of Protein Tau and Rescue of Protein Tau-induced Axonopathy by GSK-3β in GSK-3β×htau40 Double Transgenic Mice (pages 609–620)

      Kurt Spittaels, Chris Van den Haute, Jo Van Dorpe, Hugo Geerts and Fred Van Leuven

    27. Chapter 57

      Pathogenic Implication of Altered Tau Properties Caused by FTDP-17 Mutations (pages 621–629)

      P. Nacharaju, S. Yen, M. DeTure, C. Easson, M. Hutton and S.-H. Yen

    28. Chapter 58

      A Hexapeptide Motif (306VQIVYK311)-forming β Structure Induces the Aggregation of Tau Protein to Paired Helical Filaments (pages 631–640)

      M. von Bergen, J. Biernat, E.-M. Mandelkow and Eckhard Mandelkow

  7. Part V: Animal and Cellular Models

    1. Chapter 59

      Formation of Neurofibrillary Tangles in Mouse Brain (pages 641–649)

      Akihiko Takashima and Kentaro Tanemura

    2. Chapter 60

      Inducible Transgenic Expression of Wild-Type tau in H4 Neuroglioma Cells (pages 651–660)

      Michael DeTure, Li-Wen Ko, Colin Easson, Mike Hutton and Shu-Hui Yen

    3. Chapter 61

      Lewy-Like Pathology in Mice Transgenic for Mutant (A53T) and Wild-Type Human α-Synuclein (pages 661–670)

      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

    4. Chapter 62

      Somal and Neuritic Accumulation of the Parkinson's Disease-Associated Mutant [A30P]α-Synuclein in Transgenic Mice (pages 671–677)

      Philipp J. Kahle, Manuela Neumann, Laurence Ozmen, Hans A. Kretzschmar and Christian Haass

    5. Chapter 63

      Ex Vivo Transmission of Mouse-Adapted Prion Strains to N2a and GT1-7 Cell Lines (pages 679–686)

      Sylvain Lehmann, Hubert Laude, David A. Harris, Richard I. Carp, Didier Vilette, Shigeru Katamine, Jean-Yves Madec and Noriyuki Nishida

    6. Chapter 64

      In Vivo Perturbation of Lysosomal Function Promotes Neurodegeneration in the PS1M146V/APPK670N,M671L Mouse Model of Alzheimer's Disease Pathology (pages 687–695)

      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

    7. Chapter 65

      Changes in Cognitive Characteristics of Tg(APP)CRND8 Mice at Early Stages of Immunization with Beta-Amyloid Peptide (pages 697–704)

      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

  8. Part VI: Therapeutics and Therapeutic Strategies

    1. Chapter 66

      Galantamine, a Novel Treatment for Alzheimer's Disease: A Review of Long-term Benefits to Patients and Caregivers (pages 705–723)

      Pierre Tariot and Bengt Winblad

    2. Chapter 67

      Benefits of Donepezil on Cognition, Function and Neuropsychiatric Symptoms in Patients with Mild and Moderate Alzheimer's Disease over One Year (pages 725–738)

      Gunhild Waldemar, Bengt Winblad, Knut Engedal, Hilkka Soininen, Frans Verhey, Anders Wimo, Anna-Lena Wetterholm, Richard Zhang, Anders Haglund and Ponni Subbiah

    3. Chapter 68

      Characterization of Alzheimer's β-Secretase Protein BACE: Processing and Other Post-translational Modifications (pages 739–745)

      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

    4. Chapter 69

      Androgen Treatment Reduces Cognitive Deficits in Female apoE4 Transgenic Mice (pages 747–757)

      Jacob Raber, Anthony LeFevour and Lennart Mucke

    5. Chapter 70

      Studies with the Memory-Enhancing Drug AIT-082 in PC12 Cells (pages 759–767)

      Debomoy K. Lahiri, Yuan-Wen Ge and Martin R. Farlow

    6. Chapter 71

      Generation of Auto-antibodies toward Alzheimer's Disease Vaccination (pages 769–775)

      Beka Solomon and Dan Frenkel

    7. Chapter 72

      Toward the Identification of γ-Secretase: Using Transition State Analog Inhibitors (pages 777–788)

      William P. Esler, W. Taylor Kimberly, Beth L. Ostaszewski, Weiming Xia, Dennis J. Selkoe and Michael S. Wolfe

    8. Chapter 73

      Photoactivated, Active-Site-Directed γ-Secretase Inhibitors Covalently Label Presenilin 1 (pages 789–798)

      Stephen J. Gardell, Yue-Ming Li, Min Xu, Ming-Tain Lai, Qian Huang, Jose L. Castro, Jillian DiMuzio-Mower, Timothy Harrison, Colin Lellis, Alan Nadin, Joseph G. Neduvelil, R. Bruce Register, Mohinder K. Sardana, Mark S. Shearman, Xiao-Ping Shi, Adrian L. Smith, Kuo-Chang Yin and Jules A. Shafer

    9. Chapter 74

      Functional Analysis of β-Secretase Using Mutagenesis and Structural Homology Modeling (pages 799–807)

      Gwen Tatsuno, John Anderson, Jin Hong, David A. Agard, Nobuyuki Ota, Sukanto Sinha, Guriqbal Basi and Lisa McConlogue

    10. Chapter 75

      Therapeutic Approaches to Prion Diseases: In Vitro Studies with Tetracycline Compounds (pages 809–820)

      Tazeen Awan, Gianluigi Forloni, Enzio Ragg, Selina Iussich, Giacomina Rossi, Laura Colombo, Laura Girola, Tania Massignan, Orso Bugiani, Mario Salmona and Fabrizio Tagliavini

  9. Part VII: Psychosocial Care

    1. Chapter 76

      Influence of a Memory Training Program on Attention and Memory Performance of Patients with Dementia (pages 821–831)

      Tanja Bernhardt, Konrad Maurer and Lutz Frölich

    2. Chapter 77

      Prediction of Use of Emergency Community Services by Cognitively Impaired Seniors who Live Alone: Preliminary Findings of a Prospective Study (pages 833–841)

      Mary C. Tierney, Jocelyn Charles, W. Gary Snow, John P. Szalai, Susan Jaglal, Franca Spizzirri and Rory H. Fisher

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