K Iqbal
John Wiley & Sons
e druk, 2001
9780471521761
Alzheimers Disease – Advances in Etiology Pathogenesis & Therapeutics
Advances in Etiology, Pathogenesis and Therapeutics
Specificaties
Gebonden, 888 blz.
|
Engels
John Wiley & Sons |
2001
ISBN13: 9780471521761
Rubricering
Verwachte levertijd ongeveer 16 werkdagen
Gratis verzonden
Samenvatting
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.
Specificaties
Inhoudsopgave
<p>List of Contributors xii</p>
<p>Dedications xxvi</p>
<p>Scientists Honored for Pioneering Research xxix</p>
<p>Preface xxxv</p>
<p>Acknowledgments xxxvi</p>
<p>I. EPIDEMIOLOGY AND RISK FACTORS 1</p>
<p>1. The Transition from Normal Functioning to Dementia in the Aging Population 3<br />Laura Fratiglioni, Brent Small, Bengt Winblad and Lars Bäckman </p>
<p>2. Epidemiology of Alzheimer s Disease and Dementia: Advances and Challenges 11<br />Robert Katzman </p>
<p>3. Epidemiology of Dementia in Down s Syndrome 23<br />Nicole Schupf </p>
<p>II. GENETICS 31</p>
<p>4. A Genomic Search for Alzheimer s Disease Genes 33<br />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 </p>
<p>5. Candidate Genes Showing No Evidence of Association with Alzheimer s Disease: Results of the NIMH–AD Genetics Initiative 45<br />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 </p>
<p>6. Familial Alzheimer s Disease with Spastic Paraparesis Associated with a Mutation at Codon 261 of the Presenilin 1 Gene 53<br />Martin R. Farlow, Jill R. Murrell, Frederick W. Unverzagt, Michael Phillips, Masaki Takao, Christine Hulette and Bernardino Ghetti </p>
<p>7. Genetic Analysis of the Presenilin Pathway in Drosophila 61<br />Izhar Livne–Bar and Gabrielle L. Boulianne </p>
<p>8. Molecular Genetics and Transgenic Modeling of the Tauopathies 71<br />Jada Lewis, Matt Baker, Marjon Van Slegtenhorst and Mike Hutton </p>
<p>9. Regulation of Four–repeat tau Expression: Interactions between Exon and Intron Splicing Regulatory Sequences 87<br />Ian D Souza and Gerard D. Schellenberg </p>
<p>III. DIAGNOSIS AND CLINICAL COURSE 97</p>
<p>10. Preclinical Prediction of AD: Relation Between Neuropsychological and Neuroimaging Findings 99<br />Marilyn S. Albert, Ronald J. Killiany, Keith Johnson, Rudolph E. Tanzi and Kenneth Jones </p>
<p>11. Neuropsychological Detection of Preclinical Alzheimer s Disease: Results of a Neuropathological Series of Normal Controls 111<br />Kathleen A. Welsh–Bohmer, Christine Hulette, Donald Schmechel, James Burke and Ann Saunders </p>
<p>12. Potentially Reversible Conditions in Memory Clinic Patients 123<br />Anne–Mette Hejl, Peter Høgh and Gunhild Waldemar </p>
<p>13. The Alzheimer s Disease Centers Neuropsychological Database Initiative: A Resource for Alzheimer s Disease Prevention Trials 129<br />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 </p>
<p>14. Mild Cognitive Impairment: Transition from Aging to Alzheimer s Disease 141<br />Ronald C. Petersen </p>
<p>15. Brain Functional Imaging in Early and Preclinical Alzheimer s Disease 153<br />Agneta Nordberg, Vesna Jelic, Eva Arnáiz, Bengt Långström and Ove Almkvist </p>
<p>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 165<br />D. S. Wang, E. Cochran, D. Bennett, E. Mufson, C. Eckman and D. W. Dickson </p>
<p>17. Imaging the Consequences of Alzheimer s Disease Pathology 181<br />Yaakov Stern and Scott Small </p>
<p>18. Influence of apoE Genotype and PET Brain Imaging on Preclinical Prediction of Alzheimer s Disease 193<br />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 </p>
<p>19. Overview of Vascular Dementia 205<br />William R. Markesbery </p>
<p>20. Clinical and Imaging Characteristics of Vascular Dementia in a Memory Clinic 219<br />F. Pasquier, X. Douay, C. Delmaire, F. Lebert and J. P. Pruvo </p>
<p>21. MRI of Entorhinal Cortex and Hippocampus in Alzheimer s Disease, Subcortical Ischemic Vascular Dementia and Mixed Dementia 229<br />N. Schuff, A. T. Du, D. Amend, Y. Y. Hsu, M. P. Laakso, W. Jagust, H. C. Chui and M. W. Weiner </p>
<p>22. Olfactory Function and Event–related Potentials in Alzheimer s Disease 237<br />Claire Murphy and Charlie D. Morgan </p>
<p>23. Phenotypic Differences in Cholinergic Markers within the Nucleus Basalis in Individuals with Mild Cognitive Impairment 253<br />Elliott J. Mufson, Michele Gilmor, Shuang Y. Ma, Alan I. Levey and Jeffrey H. Kordower </p>
<p>24. Evaluating CNS Biomarkers for Alzheimer s Disease 265<br />John H. Growdon </p>
<p>25. CSF Markers for Early Alzheimer s Disease 275<br />Kaj Blennow, Pia Davidsson and Eugeen Vanmechelen </p>
<p>26. CSF–Phospho–tau (181P) as a Promising Marker for Discriminating Alzheimer s Disease from Dementia with Lewy Bodies 285<br />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 </p>
<p>27. Increased Levels of a Minor Glycoform of Acetylcholinesterase in Alzheimer s Disease Brain and Cerebrospinal Fluid 293<br />Javier Sáez–Valero, Su San Mok, Lisa Fodero, Alberto Marcos, Maria–Sagrario Barquero, Catriona McLean and David H. Small </p>
<p>28. Plasma b–Amyloid as a Surrogate Genetic Marker in Late–onset Alzheimer s Disease 303<br />Nilufer Ertekin Taner, Neill Graff–Radford, Linda H. Younkin, Christopher Eckman, Jennifer Adamson, Daniel J. Schaid, John Blangero, Michael Hutton and Steven G. Younkin </p>
<p>29. Levels of Total and Deposited Ab are Correlated with Dementia 311<br />S. Parvathy, J. Naslund, V. Haroutunian and J. D. Buxbaum </p>
<p>30. What Should We Tell Patients Attending a Memory Disorders Clinic About Their Diagnosis? 319<br />Conor P. Maguire and Rebecca M. Slinn </p>
<p>IV. MECHANISMS OF NEURODEGENERATION 329</p>
<p>31. Innate Immunity, Autotoxicity and Degenerative Neurologies 331<br />Patrick L. McGeer, Koju Yasojima and Edith G. McGeer </p>
<p>32. Neuroinflammatory Responses in the Alzheimer s Disease Brain Promote the Oxidative Post–translational Modification of Amyloid Deposits 341<br />Craig S. Atwood, Xudong Huang, Robert D. Moir, Mark A. Smith, Rudolph E. Tanzi, Alex E. Roher, Ashley I. Bush and George Perry </p>
<p>33. Plasma Antioxidants and Oxidative DNA Damage in Lymphocytes from Normal Aged People and Alzheimer s Disease Patients 363<br />Patrizia Mecocci, Maria Cristina Polidori, Tiziana Ingegni, Paola Mattioli, Antonio Cherubini, Marco Catani, Roberta Cecchetti and Umberto Senin </p>
<p>34. Oxidative Damage and Antioxidant Responses in Alzheimer s Disease 371<br />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 </p>
<p>35. Cyclooxygenase (COX)–2 and Clinical Progression of Alzheimer s Disease Dementia: Implications in the Role of Neuronal COX–2 in Cell Cycle 379<br />Giulio Maria Pasinetti </p>
<p>36. Parallels between the Redox Properties and Toxicity of Ab in Alzheimer s Disease and Mutant Cu/Zn–SOD in Familial Amyotrophic Lateral Sclerosis 393<br />Ashley I. Bush </p>
<p>37. b–Amyloid Toxicity: Diverse Biological Activities Drive Multiple Cellular Mechanisms 407<br />C. W. Cotman, L. Tong, A. Anderson, D. Cribbs and J. Su </p>
<p>38. Mechanisms of Ab Production and Ab Degradation: Routes to the Treatment of Alzheimer s Disease 421<br />D. J. Selkoe, W. Xia, W. T. Kimberly, K. Vekrellis, D. Walsh, W. P. Esler and M. S. Wolfe </p>
<p>39. A High Fat, High Cholesterol Diet Accelerates b–Amyloid Accumulation in the CNS of a Transgenic Mouse Model of Alzheimer s Disease 433<br />Lorenzo M. Refolo, Brian Malester, John LaFrancois, Tara Bryant–Thomas, Rong Wang, G. Stephen Tint, Kumar Sambamurti, Karen Duff and Miguel A. Pappolla </p>
<p>40. Electron Microscopy and X–ray Diffraction Studies further Confirm the Efficacy of PTI–00703TM1 (Cat s Claw Derivative) as a Potential Inhibitor of Alzheimer s b–Amyloid Protein Fibrillogenesis 449<br />Gerardo M. Castillo, Daniel A. Kirschner, Ann G. Yee and Alan D. Snow </p>
<p>41. Accelerated Ab Generation in a Cell Model of Alzheimer s Disease–related Endosomal Lysosomal System Upregulation 461<br />Paul M. Mathews, Carolyn B. Guerra, Ying Jiang, Benjamin H. Kao, Ravi Dinakar, Pankaj Mehta, Anne M. Cataldo and Ralph A. Nixon </p>
<p>42. The Amyloid Precursor Protein V717I Mutation Increases Susceptibility to Cell Death in a Cholesterol–dependent Manner 469<br />Luigi Puglielli, Laura A. MacKenzie Ingano, Rudolph E. Tanzi and Dora M. Kovacs </p>
<p>43. Intracellular and Secreted Ab42/40 Ratios Are Differently Influenced by APP Mutations 479<br />Heike S. Grimm, Stefan F. Lichtenthaler, Konrad Beyreuther and Tobias Hartmann </p>
<p>44. Familial British Dementia 487<br />Jorge Ghiso, Tamas Révész, Agueda Rostagno, Ruben Vidal, Gordon Plant and Blas Frangione </p>
<p>45. Cellular Metabolism of Familial British Dementia–associated BRI–L 495<br />Seong–Hun Kim and Sangram S. Sisodia </p>
<p>46. A Decamer Duplication in the BRI Gene Originates a de novo Amyloid Peptide that Causes Dementia in a Danish Kindred 507<br />Ruben G. Vidal, Tamas Révész, Agueda Rostagno, Toke Bek, Hans Braendgaard, Gordon Plant, Jorge Ghiso and Blas Frangione </p>
<p>47. Familial Alzheimer s Disease–linked Mutant Presenilins Attenuate Capacitative Calcium Entry 515<br />Isaac Cheng, Andrew S. Yoo, Rudolph E. Tanzi and Tae–Wan Kim </p>
<p>48. Presenilin–1 Is a Regulatory Component of the Cadherin Cell Adhesion Complex: Implications for Alzheimer s Disease 521<br />Anastasio Georgakopoulos, Philippe Marambaud, Nikolaos K. Robakis and Lia Baki </p>
<p>49. Presenilins and Notch Signaling Pathway 531<br />Weihong Song and Bruce A. Yankner </p>
<p>50. Functional Consequences of the Association of PS1 with b–Catenin 541<br />Salvador Soriano, David E. Kang, Nathalie Chevallier, Hui Zheng and Edward H. Koo </p>
<p>51. A Novel Protease Active Site Motif Conserved in Presenilins and Polytopic Bacterial Aspartyl Proteases? 549<br />Harald Steiner and Christian Haass </p>
<p>52. The Unfolded Protein Response–mediated Upregulation of BiP and CHOP Is not Affected by Presenilin Expression 559<br />Naoyuki Sato and Gopal Thinakaran </p>
<p>53. Mechanisms of a–Synuclein and NAC Fibrillogenesis 569<br />Makoto Hashimoto, Edward Rockenstein, Takato Takenouchi, Margaret Mallory and Eliezer Masliah </p>
<p>54. Neurofibrillary Degeneration: Patterns of Tau Isoform Expression 587<br />André Delacourte </p>
<p>55. Phosphorylation, Microtubule Binding and Aggregation of Tau Protein in Alzheimer s Disease 601<br />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 </p>
<p>56. Phosphorylation of Protein Tau and Rescue of Protein Tau–induced Axonopathy by GSK–3b in GSK–3b6htau40 Double Transgenic Mice 609<br />Kurt Spittaels, Chris Van den Haute, Jo Van Dorpe, Hugo Geerts and Fred Van Leuven </p>
<p>57. Pathogenic Implication of Altered Tau Properties Caused by FTDP–17 Mutations 621<br />P. Nacharaju, S. Yen, M. DeTure, C. Easson, M. Hutton and S.–H. Yen </p>
<p>58. A Hexapeptide Motif (306VQIVYK311)–forming b Structure Induces the Aggregation of Tau Protein to Paired Helical Filaments 631<br />M. von Bergen, J. Biernat, E.–M. Mandelkow and Eckhard Mandelkow </p>
<p>V. ANIMAL AND CELLULAR MODELS 641</p>
<p>59. Formation of Neurofibrillary Tangles in Mouse Brain 643<br />Akihiko Takashima and Kentaro Tanemura </p>
<p>60. Inducible Transgenic Expression of Wild–type tau in H4 Neuroglioma Cells 651<br />Michael DeTure, Li–Wen Ko, Colin Easson, Mike Hutton and Shu–Hui Yen </p>
<p>61. Lewy–like Pathology in Mice Transgenic for Mutant (A53T) and Wild–type Human a–Synuclein 661<br />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 </p>
<p>62. Somal and Neuritic Accumulation of the Parkinson s Disease–associated Mutant [A30P]a–Synuclein in Transgenic Mice 671<br />Phillipp J. Kahle, Manuela Neumann, Laurence Ozmen, Hans A. Kretzschmar and Christian Haass </p>
<p>63. Ex vivo Transmission of Mouse–adapted Prion Strains to N2a and GT1–7 Cell Lines 679<br />Sylvain Lehmann, Hubert Laude, David A. Harris, Richard I. Carp, Didier Vilette, Shigeru Katamine, Jean–Yves Madec and Noriyuki Nishida </p>
<p>64. In Vivo Perturbation of Lysosomal Function Promotes Neurodegeneration in the PS1M146V/APPK670N,M671L Mouse Model of Alzheimer s Disease Pathology 687<br />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 </p>
<p>65. Changes in Cognitive Characteristics of Tg(APP)CRND8 Mice at Early Stages of Immunization with Beta–Amyloid Peptide 697<br />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 </p>
<p>VI. THERAPEUTICS AND THERAPEUTIC STRATEGIES 705</p>
<p>66. Galantamine, a Novel Treatment for Alzheimer s Disease: A Review of Long–term Benefits to Patients and Caregivers 707<br />Pierre Tariot and Bengt Winblad </p>
<p>67. Benefits of Donepezil on Cognition, Function and Neuropsychiatric Symptoms in Patients with Mild and Moderate Alzheimer s Disease over One Year 725<br />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 </p>
<p>68. Characterization of Alzheimer s b–Secretase Protein BACE: Processing and Other Post–translational Modifications 739<br />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 </p>
<p>69. Androgen Treatment Reduces Cognitive Deficits in Female apoE4 Transgenic Mice <br />Jacob Raber, Anthony LeFevour and Lennart Mucke</p>
<p>70. Studies with the Memory–enhancing Drug AIT–082 in PC12 Cells 747<br />Debomoy K. Lahiri, Yuan–Wen Ge and Martin R. Farlow </p>
<p>71. Generation of Auto–antibodies toward Alzheimer s Disease Vaccination 759<br />Beka Solomon and Dan Frenkel </p>
<p>72. Toward the Identification of c–Secretase: Using Transition State Analog Inhibitors 777<br />William P. Esler, W. Taylor Kimberly, Beth L. Ostaszewski, Weiming Xia, Dennis J. Selkoe and Michael S. Wolfe </p>
<p>73. Photoactivated, Active–site–directed g–Secretase Inhibitors Covalently Label Presenilin 1 789<br />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 </p>
<p>74. Functional Analysis of b–Secretase Using Mutagenesis and Structural Homology Modeling 799<br />Gwen Tatsuno, John Anderson, Jin Hong, David A. Agard, Nobuyuki Ota, Sukanto Sinha, Guriqbal Basi and Lisa McConlogue </p>
<p>75. Therapeutic Approaches to Prion Diseases: In Vitro Studies with Tetracycline Compounds 809<br />Tazeen Awan, Gianluigi Forloni, Enzio Ragg, Selina Iussich, Giacomina Rossi, Laura Colombo, Laura Girola, Tania Massignan, Orso Bugiani, Mario Salmona and Fabrizio Tagliavini </p>
<p>VII. PSYCHOSOCIAL CARE 821</p>
<p>76. Influence of a Memory Training Program on Attention and Memory Performance of Patients with Dementia 823<br />Tanja Bernhardt, Konrad Maurer and Lutz Frölich </p>
<p>77. Prediction of Use of Emergency Community Services by Cognitively Impaired Seniors who Live Alone: Preliminary Findings of a Prospective Study 833<br />Mary C. Tierney, Jocelyn Charles, W. Gary Snow, John P. Szalai, Susan Jaglal, Franca Spizzirri and Rory H. Fisher </p>
<p>Index 835</p>
<p>Dedications xxvi</p>
<p>Scientists Honored for Pioneering Research xxix</p>
<p>Preface xxxv</p>
<p>Acknowledgments xxxvi</p>
<p>I. EPIDEMIOLOGY AND RISK FACTORS 1</p>
<p>1. The Transition from Normal Functioning to Dementia in the Aging Population 3<br />Laura Fratiglioni, Brent Small, Bengt Winblad and Lars Bäckman </p>
<p>2. Epidemiology of Alzheimer s Disease and Dementia: Advances and Challenges 11<br />Robert Katzman </p>
<p>3. Epidemiology of Dementia in Down s Syndrome 23<br />Nicole Schupf </p>
<p>II. GENETICS 31</p>
<p>4. A Genomic Search for Alzheimer s Disease Genes 33<br />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 </p>
<p>5. Candidate Genes Showing No Evidence of Association with Alzheimer s Disease: Results of the NIMH–AD Genetics Initiative 45<br />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 </p>
<p>6. Familial Alzheimer s Disease with Spastic Paraparesis Associated with a Mutation at Codon 261 of the Presenilin 1 Gene 53<br />Martin R. Farlow, Jill R. Murrell, Frederick W. Unverzagt, Michael Phillips, Masaki Takao, Christine Hulette and Bernardino Ghetti </p>
<p>7. Genetic Analysis of the Presenilin Pathway in Drosophila 61<br />Izhar Livne–Bar and Gabrielle L. Boulianne </p>
<p>8. Molecular Genetics and Transgenic Modeling of the Tauopathies 71<br />Jada Lewis, Matt Baker, Marjon Van Slegtenhorst and Mike Hutton </p>
<p>9. Regulation of Four–repeat tau Expression: Interactions between Exon and Intron Splicing Regulatory Sequences 87<br />Ian D Souza and Gerard D. Schellenberg </p>
<p>III. DIAGNOSIS AND CLINICAL COURSE 97</p>
<p>10. Preclinical Prediction of AD: Relation Between Neuropsychological and Neuroimaging Findings 99<br />Marilyn S. Albert, Ronald J. Killiany, Keith Johnson, Rudolph E. Tanzi and Kenneth Jones </p>
<p>11. Neuropsychological Detection of Preclinical Alzheimer s Disease: Results of a Neuropathological Series of Normal Controls 111<br />Kathleen A. Welsh–Bohmer, Christine Hulette, Donald Schmechel, James Burke and Ann Saunders </p>
<p>12. Potentially Reversible Conditions in Memory Clinic Patients 123<br />Anne–Mette Hejl, Peter Høgh and Gunhild Waldemar </p>
<p>13. The Alzheimer s Disease Centers Neuropsychological Database Initiative: A Resource for Alzheimer s Disease Prevention Trials 129<br />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 </p>
<p>14. Mild Cognitive Impairment: Transition from Aging to Alzheimer s Disease 141<br />Ronald C. Petersen </p>
<p>15. Brain Functional Imaging in Early and Preclinical Alzheimer s Disease 153<br />Agneta Nordberg, Vesna Jelic, Eva Arnáiz, Bengt Långström and Ove Almkvist </p>
<p>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 165<br />D. S. Wang, E. Cochran, D. Bennett, E. Mufson, C. Eckman and D. W. Dickson </p>
<p>17. Imaging the Consequences of Alzheimer s Disease Pathology 181<br />Yaakov Stern and Scott Small </p>
<p>18. Influence of apoE Genotype and PET Brain Imaging on Preclinical Prediction of Alzheimer s Disease 193<br />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 </p>
<p>19. Overview of Vascular Dementia 205<br />William R. Markesbery </p>
<p>20. Clinical and Imaging Characteristics of Vascular Dementia in a Memory Clinic 219<br />F. Pasquier, X. Douay, C. Delmaire, F. Lebert and J. P. Pruvo </p>
<p>21. MRI of Entorhinal Cortex and Hippocampus in Alzheimer s Disease, Subcortical Ischemic Vascular Dementia and Mixed Dementia 229<br />N. Schuff, A. T. Du, D. Amend, Y. Y. Hsu, M. P. Laakso, W. Jagust, H. C. Chui and M. W. Weiner </p>
<p>22. Olfactory Function and Event–related Potentials in Alzheimer s Disease 237<br />Claire Murphy and Charlie D. Morgan </p>
<p>23. Phenotypic Differences in Cholinergic Markers within the Nucleus Basalis in Individuals with Mild Cognitive Impairment 253<br />Elliott J. Mufson, Michele Gilmor, Shuang Y. Ma, Alan I. Levey and Jeffrey H. Kordower </p>
<p>24. Evaluating CNS Biomarkers for Alzheimer s Disease 265<br />John H. Growdon </p>
<p>25. CSF Markers for Early Alzheimer s Disease 275<br />Kaj Blennow, Pia Davidsson and Eugeen Vanmechelen </p>
<p>26. CSF–Phospho–tau (181P) as a Promising Marker for Discriminating Alzheimer s Disease from Dementia with Lewy Bodies 285<br />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 </p>
<p>27. Increased Levels of a Minor Glycoform of Acetylcholinesterase in Alzheimer s Disease Brain and Cerebrospinal Fluid 293<br />Javier Sáez–Valero, Su San Mok, Lisa Fodero, Alberto Marcos, Maria–Sagrario Barquero, Catriona McLean and David H. Small </p>
<p>28. Plasma b–Amyloid as a Surrogate Genetic Marker in Late–onset Alzheimer s Disease 303<br />Nilufer Ertekin Taner, Neill Graff–Radford, Linda H. Younkin, Christopher Eckman, Jennifer Adamson, Daniel J. Schaid, John Blangero, Michael Hutton and Steven G. Younkin </p>
<p>29. Levels of Total and Deposited Ab are Correlated with Dementia 311<br />S. Parvathy, J. Naslund, V. Haroutunian and J. D. Buxbaum </p>
<p>30. What Should We Tell Patients Attending a Memory Disorders Clinic About Their Diagnosis? 319<br />Conor P. Maguire and Rebecca M. Slinn </p>
<p>IV. MECHANISMS OF NEURODEGENERATION 329</p>
<p>31. Innate Immunity, Autotoxicity and Degenerative Neurologies 331<br />Patrick L. McGeer, Koju Yasojima and Edith G. McGeer </p>
<p>32. Neuroinflammatory Responses in the Alzheimer s Disease Brain Promote the Oxidative Post–translational Modification of Amyloid Deposits 341<br />Craig S. Atwood, Xudong Huang, Robert D. Moir, Mark A. Smith, Rudolph E. Tanzi, Alex E. Roher, Ashley I. Bush and George Perry </p>
<p>33. Plasma Antioxidants and Oxidative DNA Damage in Lymphocytes from Normal Aged People and Alzheimer s Disease Patients 363<br />Patrizia Mecocci, Maria Cristina Polidori, Tiziana Ingegni, Paola Mattioli, Antonio Cherubini, Marco Catani, Roberta Cecchetti and Umberto Senin </p>
<p>34. Oxidative Damage and Antioxidant Responses in Alzheimer s Disease 371<br />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 </p>
<p>35. Cyclooxygenase (COX)–2 and Clinical Progression of Alzheimer s Disease Dementia: Implications in the Role of Neuronal COX–2 in Cell Cycle 379<br />Giulio Maria Pasinetti </p>
<p>36. Parallels between the Redox Properties and Toxicity of Ab in Alzheimer s Disease and Mutant Cu/Zn–SOD in Familial Amyotrophic Lateral Sclerosis 393<br />Ashley I. Bush </p>
<p>37. b–Amyloid Toxicity: Diverse Biological Activities Drive Multiple Cellular Mechanisms 407<br />C. W. Cotman, L. Tong, A. Anderson, D. Cribbs and J. Su </p>
<p>38. Mechanisms of Ab Production and Ab Degradation: Routes to the Treatment of Alzheimer s Disease 421<br />D. J. Selkoe, W. Xia, W. T. Kimberly, K. Vekrellis, D. Walsh, W. P. Esler and M. S. Wolfe </p>
<p>39. A High Fat, High Cholesterol Diet Accelerates b–Amyloid Accumulation in the CNS of a Transgenic Mouse Model of Alzheimer s Disease 433<br />Lorenzo M. Refolo, Brian Malester, John LaFrancois, Tara Bryant–Thomas, Rong Wang, G. Stephen Tint, Kumar Sambamurti, Karen Duff and Miguel A. Pappolla </p>
<p>40. Electron Microscopy and X–ray Diffraction Studies further Confirm the Efficacy of PTI–00703TM1 (Cat s Claw Derivative) as a Potential Inhibitor of Alzheimer s b–Amyloid Protein Fibrillogenesis 449<br />Gerardo M. Castillo, Daniel A. Kirschner, Ann G. Yee and Alan D. Snow </p>
<p>41. Accelerated Ab Generation in a Cell Model of Alzheimer s Disease–related Endosomal Lysosomal System Upregulation 461<br />Paul M. Mathews, Carolyn B. Guerra, Ying Jiang, Benjamin H. Kao, Ravi Dinakar, Pankaj Mehta, Anne M. Cataldo and Ralph A. Nixon </p>
<p>42. The Amyloid Precursor Protein V717I Mutation Increases Susceptibility to Cell Death in a Cholesterol–dependent Manner 469<br />Luigi Puglielli, Laura A. MacKenzie Ingano, Rudolph E. Tanzi and Dora M. Kovacs </p>
<p>43. Intracellular and Secreted Ab42/40 Ratios Are Differently Influenced by APP Mutations 479<br />Heike S. Grimm, Stefan F. Lichtenthaler, Konrad Beyreuther and Tobias Hartmann </p>
<p>44. Familial British Dementia 487<br />Jorge Ghiso, Tamas Révész, Agueda Rostagno, Ruben Vidal, Gordon Plant and Blas Frangione </p>
<p>45. Cellular Metabolism of Familial British Dementia–associated BRI–L 495<br />Seong–Hun Kim and Sangram S. Sisodia </p>
<p>46. A Decamer Duplication in the BRI Gene Originates a de novo Amyloid Peptide that Causes Dementia in a Danish Kindred 507<br />Ruben G. Vidal, Tamas Révész, Agueda Rostagno, Toke Bek, Hans Braendgaard, Gordon Plant, Jorge Ghiso and Blas Frangione </p>
<p>47. Familial Alzheimer s Disease–linked Mutant Presenilins Attenuate Capacitative Calcium Entry 515<br />Isaac Cheng, Andrew S. Yoo, Rudolph E. Tanzi and Tae–Wan Kim </p>
<p>48. Presenilin–1 Is a Regulatory Component of the Cadherin Cell Adhesion Complex: Implications for Alzheimer s Disease 521<br />Anastasio Georgakopoulos, Philippe Marambaud, Nikolaos K. Robakis and Lia Baki </p>
<p>49. Presenilins and Notch Signaling Pathway 531<br />Weihong Song and Bruce A. Yankner </p>
<p>50. Functional Consequences of the Association of PS1 with b–Catenin 541<br />Salvador Soriano, David E. Kang, Nathalie Chevallier, Hui Zheng and Edward H. Koo </p>
<p>51. A Novel Protease Active Site Motif Conserved in Presenilins and Polytopic Bacterial Aspartyl Proteases? 549<br />Harald Steiner and Christian Haass </p>
<p>52. The Unfolded Protein Response–mediated Upregulation of BiP and CHOP Is not Affected by Presenilin Expression 559<br />Naoyuki Sato and Gopal Thinakaran </p>
<p>53. Mechanisms of a–Synuclein and NAC Fibrillogenesis 569<br />Makoto Hashimoto, Edward Rockenstein, Takato Takenouchi, Margaret Mallory and Eliezer Masliah </p>
<p>54. Neurofibrillary Degeneration: Patterns of Tau Isoform Expression 587<br />André Delacourte </p>
<p>55. Phosphorylation, Microtubule Binding and Aggregation of Tau Protein in Alzheimer s Disease 601<br />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 </p>
<p>56. Phosphorylation of Protein Tau and Rescue of Protein Tau–induced Axonopathy by GSK–3b in GSK–3b6htau40 Double Transgenic Mice 609<br />Kurt Spittaels, Chris Van den Haute, Jo Van Dorpe, Hugo Geerts and Fred Van Leuven </p>
<p>57. Pathogenic Implication of Altered Tau Properties Caused by FTDP–17 Mutations 621<br />P. Nacharaju, S. Yen, M. DeTure, C. Easson, M. Hutton and S.–H. Yen </p>
<p>58. A Hexapeptide Motif (306VQIVYK311)–forming b Structure Induces the Aggregation of Tau Protein to Paired Helical Filaments 631<br />M. von Bergen, J. Biernat, E.–M. Mandelkow and Eckhard Mandelkow </p>
<p>V. ANIMAL AND CELLULAR MODELS 641</p>
<p>59. Formation of Neurofibrillary Tangles in Mouse Brain 643<br />Akihiko Takashima and Kentaro Tanemura </p>
<p>60. Inducible Transgenic Expression of Wild–type tau in H4 Neuroglioma Cells 651<br />Michael DeTure, Li–Wen Ko, Colin Easson, Mike Hutton and Shu–Hui Yen </p>
<p>61. Lewy–like Pathology in Mice Transgenic for Mutant (A53T) and Wild–type Human a–Synuclein 661<br />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 </p>
<p>62. Somal and Neuritic Accumulation of the Parkinson s Disease–associated Mutant [A30P]a–Synuclein in Transgenic Mice 671<br />Phillipp J. Kahle, Manuela Neumann, Laurence Ozmen, Hans A. Kretzschmar and Christian Haass </p>
<p>63. Ex vivo Transmission of Mouse–adapted Prion Strains to N2a and GT1–7 Cell Lines 679<br />Sylvain Lehmann, Hubert Laude, David A. Harris, Richard I. Carp, Didier Vilette, Shigeru Katamine, Jean–Yves Madec and Noriyuki Nishida </p>
<p>64. In Vivo Perturbation of Lysosomal Function Promotes Neurodegeneration in the PS1M146V/APPK670N,M671L Mouse Model of Alzheimer s Disease Pathology 687<br />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 </p>
<p>65. Changes in Cognitive Characteristics of Tg(APP)CRND8 Mice at Early Stages of Immunization with Beta–Amyloid Peptide 697<br />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 </p>
<p>VI. THERAPEUTICS AND THERAPEUTIC STRATEGIES 705</p>
<p>66. Galantamine, a Novel Treatment for Alzheimer s Disease: A Review of Long–term Benefits to Patients and Caregivers 707<br />Pierre Tariot and Bengt Winblad </p>
<p>67. Benefits of Donepezil on Cognition, Function and Neuropsychiatric Symptoms in Patients with Mild and Moderate Alzheimer s Disease over One Year 725<br />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 </p>
<p>68. Characterization of Alzheimer s b–Secretase Protein BACE: Processing and Other Post–translational Modifications 739<br />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 </p>
<p>69. Androgen Treatment Reduces Cognitive Deficits in Female apoE4 Transgenic Mice <br />Jacob Raber, Anthony LeFevour and Lennart Mucke</p>
<p>70. Studies with the Memory–enhancing Drug AIT–082 in PC12 Cells 747<br />Debomoy K. Lahiri, Yuan–Wen Ge and Martin R. Farlow </p>
<p>71. Generation of Auto–antibodies toward Alzheimer s Disease Vaccination 759<br />Beka Solomon and Dan Frenkel </p>
<p>72. Toward the Identification of c–Secretase: Using Transition State Analog Inhibitors 777<br />William P. Esler, W. Taylor Kimberly, Beth L. Ostaszewski, Weiming Xia, Dennis J. Selkoe and Michael S. Wolfe </p>
<p>73. Photoactivated, Active–site–directed g–Secretase Inhibitors Covalently Label Presenilin 1 789<br />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 </p>
<p>74. Functional Analysis of b–Secretase Using Mutagenesis and Structural Homology Modeling 799<br />Gwen Tatsuno, John Anderson, Jin Hong, David A. Agard, Nobuyuki Ota, Sukanto Sinha, Guriqbal Basi and Lisa McConlogue </p>
<p>75. Therapeutic Approaches to Prion Diseases: In Vitro Studies with Tetracycline Compounds 809<br />Tazeen Awan, Gianluigi Forloni, Enzio Ragg, Selina Iussich, Giacomina Rossi, Laura Colombo, Laura Girola, Tania Massignan, Orso Bugiani, Mario Salmona and Fabrizio Tagliavini </p>
<p>VII. PSYCHOSOCIAL CARE 821</p>
<p>76. Influence of a Memory Training Program on Attention and Memory Performance of Patients with Dementia 823<br />Tanja Bernhardt, Konrad Maurer and Lutz Frölich </p>
<p>77. Prediction of Use of Emergency Community Services by Cognitively Impaired Seniors who Live Alone: Preliminary Findings of a Prospective Study 833<br />Mary C. Tierney, Jocelyn Charles, W. Gary Snow, John P. Szalai, Susan Jaglal, Franca Spizzirri and Rory H. Fisher </p>
<p>Index 835</p>