Alexander Disease: A Genetic Disorder of Astrocytes

  • Michael Brenner
  • James E. Goldman
  • Roy A. Quinlan
  • Albee Messing

24.1 Introduction

This volume documents the multiple roles astrocytes perform in the normal development and function of the central nervous system (CNS). A nagging question has been that if these roles are as critical as assumed, why have genetic diseases of astrocyte dysfunction not been identified to take their place next to those due to defects in neurons and oligodendrocytes? An explanation casually offered is that these functions are so important that their loss would be embryonic lethal, and thus not be detected. But this is not a satisfactory answer, as mutations that result in a partial loss of function would still be expected. Here we describe the first discovered instance of a primary astrogliopathy, in which a defect in astrocytes indeed results in a human disorder – Alexander disease. Fittingly, the gene encoding glial fibrillary acidic protein (GFAP), the intermediate filament protein that has been the standard marker for astrocytes in both basic and clinical studies, has...


Glial Fibrillary Acidic Protein Intermediate Filament Glial Fibrillary Acidic Protein Expression Glial Fibrillary Acidic Protein Level Alexander Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Central nervous system


Cerebrospinal fluid


Electron microscopy


γ-Amino butyric acid


Glutamic acid decarboxylase


Glial fibrillary acidic protein


Green fluorescent protein


Glial l-glutamate transporter


Human GFAP


c-Jun amino-terminal kinase


Mendelian inheritance in man


Magnetic resonance imaging


Sodium dodecyl sulfate polyacrylamide gel electrophoresis


Tumor necrosis factor α


Thyrotropin releasing hormone



We thank Daniel M. Bolt for statistical assistance, Marjo van der Knaap for permission to use Fig. 24.1, Anne B. Johnson for permission to use Fig. 24.2, and Rong Li for the images in Fig. 24.7. The authors would also like to thank the editors for giving them the opportunity to write this extensive, and final, review of their careers. One more would be too many. This work was supported by NINDS grant P01NS42803.


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Michael Brenner
    • 1
  • James E. Goldman
    • 1
  • Roy A. Quinlan
    • 1
  • Albee Messing
    • 1
  1. 1.Department of NeurobiologyEvelyn F. McKnight Brain Institute, Center for Glial Biology in Medicine, University of Alabama BirminghamBirminghamUSA

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