Molecular Basis of Dementia

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Product Details

Table of Contents

Preface xi
Part I. [alpha]-Synuclein in Neurodegenerative Disease
Clinical Lewy Body Syndromes 1
Clinical and Neuropathological Correlates of Dementia with Lewy Bodies 9
The [alpha]-Synucleinopathies: Parkinson's Disease, Dementia with Lewy Bodies, and Multiple System Atrophy 16
Genetics of Parkinson's Disease 28
Physiology and Pathophysiology of [alpha]-Synuclein: Cell Culture and Transgenic Animal Models Based on a Parkinson's Disease-associated Protein 33
Accelerated Oligomerization by Parkinson's Disease Linked [alpha]-Synuclein Mutants 42
Part II. Novel Mutations in Dementia
Classification and Description of Frontotemporal Dementias 46
Progress in Hereditary Tauopathies: A Mutation in the Tau Gene (G389R) Causes a Pick Disease-like Syndrome 52
Molecular Genetics of Chromosome 17 Tauopathies
Tau Gene Mutations in Frontotemporal Dementia and Parkinsonism Linked to Chromosome 17 (FTDP-17): Their Relevance for Understanding the Neurodegenerative Process 74
Amyloidogenesis in Familial British Dementia Is Associated with a Genetic Defect on Chromosome 13 84
Familial British Dementia: Expression and Metabolism of BRI 93
High Frequency of Mutations in Four Different Disease Genes in Early-Onset Dementia 100
Pathological Tau Phenotypes: The Weight of Mutations, Polymorphisms, and Differential Neuronal Vulnerabilities 107
Coexistent Tau and Amyloid Pathology in Hereditary Frontotemporal Dementia with Tau Mutations 115
The Clinical Spectrum of Guam ALS and Parkinson-Dementia Complex: 1997-1999 120
Part III. Transgenic and Knockout Approaches to Neurodegenerative Diseases
In Vivo Analysis of Wild-type and FTDP-17 Tau Transgenic Mice 126
Pathogenic Mechanisms of Alzheimer's Disease Analyzed in the APP23 Transgenic Mouse Model 134
Prions: Pathogenesis and Reverse Genetics 140
Presenilin Function in APP Processing 158
Role of Presenilin-1 in Murine Neural Development 165
Modulation of A[beta] Deposition in APP Transgenic Mice by an Apolipoprotein E Null Background 171
The Value of Transgenic Models for the Study of Neurodegenerative Diseases 179
Part IV. Proteases in Alzheimer's Disease
Identifying Proteases That Cleave APP 192
Toward the Characterization and Identification of [gamma]-Secretases Using Transition-state Analogue Inhibitor 197
Recent Advances in the Understanding of the Processing of APP to Beta Amyloid Peptide 206
Presenilin-1: A Component of Synaptic and Endothelial Adherens Junctions 209
[alpha]-Secretase Activity of the Disintegrin Metalloprotease ADAM 10: Influences of Domain Structure 215
Rapid Notchl Nuclear Translocation after Ligand Binding Depends on Presenilin-associated [gamma]-Secretase Activity 223
GSK3[beta] Forms a Tetrameric Complex with Endogenous PS1-CTF/NTF and [beta]-Catenin: Effects of the D257/D385A and FAD-linked Mutations 227
An Empirical Model of [gamma]-Secretase Activity 233
Overexpression of Presenilin-2 Enhances Apoptotic Death of Cultured Cortical Neurons 241
[alpha]1-Antichymotrypsin Inhibits A[beta] Degradation in Vitro and in Vivo 245
Activated Mitogenic Signaling Induces a Process of Dedifferentiation in Alzheimer's Disease That Eventually Results in Cell Death 249
Inhibition of the Neuronal Insulin Receptor: An in Vivo Model for Sporadic Alzheimer Disease? 256
Cytoplasmic Presenilin Aggregates in Proteasome Inhibitor-treated Cells 259
Part V. Therapies for Alzheimer's Disease beyond AChE Inhibitors
Regulation of APP Synthesis and Secretion by Neuroimmunophilin Ligands and Cyclooxygenase Inhibitors 261
A[beta] Modulation: The Next Generation of AD Therapeutics 269
Prevention and Reduction of AD-type Pathology in DPAPP Mice Immunized with A[beta subscript 1-42] 274
Treatment with the Selective Muscarinic Agonist Talsaclidine Decreases Cerebrospinal Fluid Levels of Total Amyloid [beta]-Peptide in Patients with Alzheimer's Disease 285
Metal Chelation as a Potential Therapy for Alzheimer's Disease 292
Regulation of Gene Expression by Muscarinic Acetylcholine Receptors: A Comprehensive Approach for the Identification of Regulated Genes 305
Cholinergic Modulation of Amyloid Processing and Dementia in Animal Models of Alzheimer's Disease 309
M1 Muscarinic Agonists as Potential Disease-Modifying Agents in Alzheimer's Disease: Rationale and Perspectives 315
Cholinesterase Inhibitors Stabilize Alzheimer's Disease 321
Nasal A[beta] Treatment Induces Anti-A[beta] Antibody Production and Decreases Cerebral Amyloid Burden in PD-APP Mice 328
Cytidine (5')Diphosphocholine Modulates Dopamine K[superscript +]-evoked Release in Striatum Measured by Microdialysis 332
Index of Contributors 337
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