Linked e-resources
Details
Table of Contents
1. History and classical concepts (the pre-genetic era)
1.1 The first case and early history
1.2 What are Rosenthal fibers?
1.3 What are astrocytes?
1.4 Clinical spectrum of Alexander disease circa 2001
1.5 MRI criteria for diagnosis
1.6 Population characteristics
2. Genetics of Alexander disease
2.1 Initial discovery of GFAP and its impact in neuroscience and neuropathology
2.2 Link to Alexander disease
2.3 Overview of current genetics
2.4 What about Alexander disease patients whose GFAP sequence is normal?
2.5 Issues in genetic counseling
3. Expansion of clinical phenotype and remaining gaps in understanding
3.1 Classification systems
3.2 Does Alexander disease always involve abnormalities of white matter?
3.3 Is the intellectual disability in Alexander disease unique?
3.4 The need for natural history studies of Alexander disease
3.5 Common misconceptions from the early literature
3.6 Gaps in understanding of the clinical phenotype
4. Mechanisms of disease
4.1 GFAP and evolution
4.2 Other cell types do express GFAP - are they affected as well?
4.3 Comparisons with disorders of other intermediate filaments
4.4 Model systems for study
4.4.1 Cell-free systems
4.4.2 Cell cultures
4.4.3 Does Alexander disease occur in other animal species?
4.4.4 Engineered animal models
4.5 How do GFAP variants cause disease?
4.6 Are astrocytes lost?
4.7 Are Rosenthal fibers toxic for astrocytes?
4.8 Can one have Alexander disease without Rosenthal fibers?
4.9 Can one have Rosenthal fibers without Alexander disease?
4.10 What does Alexander disease have in common with other neurological disorders?
5. In search of treatments
5.1 Past approaches
5.2 Ideas from genetics
5.2.1 aB-crystallin
5.2.2 Nrf2
5.3 Tests of specific candidate drugs
5.4 Unbiased drug screens
5.5 Antisense therapy
5.6 Is there a role for stem cells and cell transplantation?
6. Conclusions
6.1 Variability - why is the disease severe in some, and much milder in others?
6.1.1 Environmental modifiers
6.1.2 Genetic modifiers
6.2 Can we cure Alexander disease?
Other resources and organizations
Acknowledgments
References
Glossary
Author biography.
1.1 The first case and early history
1.2 What are Rosenthal fibers?
1.3 What are astrocytes?
1.4 Clinical spectrum of Alexander disease circa 2001
1.5 MRI criteria for diagnosis
1.6 Population characteristics
2. Genetics of Alexander disease
2.1 Initial discovery of GFAP and its impact in neuroscience and neuropathology
2.2 Link to Alexander disease
2.3 Overview of current genetics
2.4 What about Alexander disease patients whose GFAP sequence is normal?
2.5 Issues in genetic counseling
3. Expansion of clinical phenotype and remaining gaps in understanding
3.1 Classification systems
3.2 Does Alexander disease always involve abnormalities of white matter?
3.3 Is the intellectual disability in Alexander disease unique?
3.4 The need for natural history studies of Alexander disease
3.5 Common misconceptions from the early literature
3.6 Gaps in understanding of the clinical phenotype
4. Mechanisms of disease
4.1 GFAP and evolution
4.2 Other cell types do express GFAP - are they affected as well?
4.3 Comparisons with disorders of other intermediate filaments
4.4 Model systems for study
4.4.1 Cell-free systems
4.4.2 Cell cultures
4.4.3 Does Alexander disease occur in other animal species?
4.4.4 Engineered animal models
4.5 How do GFAP variants cause disease?
4.6 Are astrocytes lost?
4.7 Are Rosenthal fibers toxic for astrocytes?
4.8 Can one have Alexander disease without Rosenthal fibers?
4.9 Can one have Rosenthal fibers without Alexander disease?
4.10 What does Alexander disease have in common with other neurological disorders?
5. In search of treatments
5.1 Past approaches
5.2 Ideas from genetics
5.2.1 aB-crystallin
5.2.2 Nrf2
5.3 Tests of specific candidate drugs
5.4 Unbiased drug screens
5.5 Antisense therapy
5.6 Is there a role for stem cells and cell transplantation?
6. Conclusions
6.1 Variability - why is the disease severe in some, and much milder in others?
6.1.1 Environmental modifiers
6.1.2 Genetic modifiers
6.2 Can we cure Alexander disease?
Other resources and organizations
Acknowledgments
References
Glossary
Author biography.