Pathobiology of Alzheimer's Disease
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Table of contents
- Contentsv
- Contributorsix
- Series Prefacexi
- Prefacexiii
- Chapter 1. Plaques and tangles in Alzheimer’s disease: a historical introduction1
- 1.1 The Alzheimer century1
- 1.2 Early history of dementia and Alzheimer’s disease2
- 1.3 Alois Alzheimer and his disease4
- 1.4 Further progress with plaques and tangles5
- References6
- Chapter 2. Structure, biochemistry and molecular pathogenesis of paired helical filaments in Alzheim9
- 2.1 The anatomy of neurofibrillary degeneration9
- 2.2 The ultrastructure of neurofibrillary tangles12
- 2.3 Molecular analysis of the PHF core13
- 2.4 Development and application of quantitative methods for measuring PHF-bound tau18
- 2.5 Quantitative studies of tau protein in PHF preparations21
- 2.6 Phosphorylation of tau protein26
- 2.7 Immunohistochemical studies of altered tau processing in Alzheimer’s disease28
- 2.8 Aetiology of abnormal tau processing in Alzheimer’s disease – insights from other neurodegen30
- 2.9 Conclusion32
- References35
- Chapter 3. Tau proteins and their significance in the pathobiology of Alzheimer’s disease41
- Summary41
- 3.1 Introduction42
- 3.2 Molecular components of the pathological signatures of Alzheimer’s disease44
- 3.3 Formation of neurofibrillary lesions from derivatized forms of CNS τ (PHFτ) in Alzheimer’s d47
- 3.4 Kinases and phosphatases potentially involved in the conversion of normal CNS τ into PHFτ in A50
- 3.5 Functional implications of neurofibraary lesions in Alzheimer’s disease51
- 3.6 Concluding remarks54
- Acknowledgements54
- References54
- Chapter 4. The genetics of Alzheimer’s disease and mutations in the amyloid β-protein precursor g59
- Summary59
- 4.1 Is Alzheimer’s disease a genetic disease?60
- 4.2 Clinical and pathological features of Alzheimer’s disease60
- 4.3 Other cerebral amyloidoses61
- 4.4 Down’s syndrome and Alzheimer’s disease62
- 4.5 Linkage to chromosome 2162
- 4.6 Exclusion of the APP gene63
- 4.7 Mutations in the APP gene64
- 4.8 Importance of APP mutations in Alzheimer’s disease69
- 4.9 Pathogenicity of the APP mutations70
- 4.10 Clinical and pathological features associated with APP mutations71
- 4.11 Linkage of AD to other loci73
- 4.12 Conclusions75
- References75
- Chapter 5. Transcriptional control of the amyloid β-protein precursor expression79
- Summary79
- 5.1 Cell and tissue distribution of APP and mRNA80
- 5.2 APP expression in Alzheimer’s disease80
- 5.3 APP expression in Down’s syndrome80
- 5.4 APP expression in response to activating factors81
- 5.5 Sequence elements of potential regulatory significance in the APP promoter82
- 5.6 Analysis of APP promoter regulation85
- 5.7 Conclusion93
- Addendum95
- References96
- Chapter 6. Post-translational control of the amyloid β-protein precursor processing99
- 6.1 Introduction99
- 6.2 Protein kinase C and APP101
- 6.3 Regulation of APP processing by intracellular messengers105
- 6.4 Regulation of APP processing by calcium107
- 6.5 Regulation of APP processing in vivo109
- 6.6 Summary110
- References111
- Chapter 7. Processing of the amyloid β-protein precursor115
- 7.1 Amyloid and Alzheimer’s disease115
- 7.2 Aβ deposition in Alzheimer’s disease116
- 7.3 The APP117
- 7.4 Genetic evidence for a causal role of amyloid deposition in Alzheimer’s disease119
- 7.5 APP processing121
- 7.6 Implications for future research on Alzheimer’s disease132
- References139
- Chapter 8. Neurotoxicity of amyloid β-protein and the amyloid β-protein precursor145
- 8.1 Introduction145
- 8.2 Neurotoxicity of Aβ and related peptides146
- 8.3 Neurotoxicity of carboxyl terminal fragments of APP150
- 8.4 Neurotoxicity of abnormally metabolized APP fragments152
- 8.5 An alternative hypothesis for amyloid-associated neuronal death in AD160
- 8.6 Conclusion163
- References164
- Chapter 9. Biological functions of the amyloid β-protein precursor167
- 9.1 Introduction167
- 9.2 Characterization and distribution of APP168
- 9.3 Potential physiological roles of APP173
- 9.4 Conclusions179
- References180
- Chapter 10. Cellular and animal models of amyloid β-protein amyloidosis183
- 10.1 Introduction183
- 10.2 Biology of APP and Aβ184
- 10.3 Animal models of AD186
- Acknowledgements189
- References189
- Chapter 11. Relationship of plaques and tangles to Alzheimer’s disease phenotype193
- 11.1 Introduction193
- 11.2 Clinical phenotype194
- 11.3 Plaques, tangles and Alzheimer’s disease200
- 11.4 Clinicopathological correlations in AD215
- 11.5 Conclusions217
- Acknowledgements218
- References218
- Chapter 12. Apolipoprotein E and Alzheimer’s disease225
- 12.1 Apolipoprotein E225
- 12.2 ApoE and LDL receptor: a role in PNS regeneration and CNS reinnervation227
- 12.3 Synaptic remodelling and Alzheimer’s disease: a role for ApoE?231
- 12.4 Alzheimer’s disease and ApoE4235
- 12.5 ApoE4 and neuropathological features237
- 12.6 ApoE4 and cholinergic deficits239
- 12.7 Conclusion243
- References243
- Index247
- Color Plate Section257
Neuroscience Perspectives provides multidisciplinary reviews of topics in one of the most diverse and rapidly advancing fields in the life sciences.
Whether you are a new recruit to neuroscience, or an established expert, look to this series for 'one-stop' sources of the historical, physiological, pharmacological, biochemical, molecular biological and therapeutic aspects of chosen research areas.
The last decade has seen tremendous advances in our understanding of the pathobiology of Alzheimer's disease. These will lead to the first generation of drugs aimed at prevention rather than cure. This book covers some of the most important and exciting of these advances, with chapters written by many of the leading researchers in the field.
With genetic studies as a backbone to this volume many chapters are devoted to the function and regulation of amyloid b-protein precursor (APP) and apolipoprotein E (ApoE). Other chapters describe cell biological approaches helping to piece together the link between the genetic alterations and the phenotype we call Alzheimer's disease.
Although APP and its proteolytic cleavage product, amyloid b-protein, do not answer all the questions, detailed research into this system has undoubtedly increased our knowledge of the pathobiology of AD and has lead to the identification of other risk factors. Understanding the role of ApoE in the pathology of Alzheimer's disease promises to open a whole new field in AD research.
*
* Reviews the current knowledge of the pathogenesis of Alzheimer's Disease from a clinical perspective to a genetic and cell biological perspective
* A comprehensive description of the role of amyloid B-protein precursor in Alzheimer's disease.
* Up-to-date research data
* Clear illustrations complement the text
Whether you are a new recruit to neuroscience, or an established expert, look to this series for 'one-stop' sources of the historical, physiological, pharmacological, biochemical, molecular biological and therapeutic aspects of chosen research areas.
The last decade has seen tremendous advances in our understanding of the pathobiology of Alzheimer's disease. These will lead to the first generation of drugs aimed at prevention rather than cure. This book covers some of the most important and exciting of these advances, with chapters written by many of the leading researchers in the field.
With genetic studies as a backbone to this volume many chapters are devoted to the function and regulation of amyloid b-protein precursor (APP) and apolipoprotein E (ApoE). Other chapters describe cell biological approaches helping to piece together the link between the genetic alterations and the phenotype we call Alzheimer's disease.
Although APP and its proteolytic cleavage product, amyloid b-protein, do not answer all the questions, detailed research into this system has undoubtedly increased our knowledge of the pathobiology of AD and has lead to the identification of other risk factors. Understanding the role of ApoE in the pathology of Alzheimer's disease promises to open a whole new field in AD research.
*
* Reviews the current knowledge of the pathogenesis of Alzheimer's Disease from a clinical perspective to a genetic and cell biological perspective
* A comprehensive description of the role of amyloid B-protein precursor in Alzheimer's disease.
* Up-to-date research data
* Clear illustrations complement the text