Alexander disease (AxD) is a neurodegenerative disorder that primarily affects the white matter of the central nervous system (CNS) [1–5]. It was first reported in 1949 by W. Stewart Alexander in a 15-month-old boy with megalencephaly, hydrocephalus and psychomotor retardation. The brain pathology of the boy showed “progressive fibrinoid degeneration of fibrillary astrocytes,” [6] which was later identified as Rosenthal fibers that were initially described by Werner Rosenthal in ependymoma in 1898 [7]. Rosenthal fibers are homogeneous eosinophilic inclusions stained by hematoxylin and eosin, and consist mainly of glial fibrillary acidic protein (GFAP), αB-crystallin, heat shock protein (HSP) 27 and cyclin D2 [2, 3, 5]. Messing and colleagues reported that AxD was elicited by mutations in the gene encoding GFAP, a type III intermediate filament predominantly found in astrocytes. They suggested that the mutations act in a gain-of-function fashion based on their finding that the phenotypes of Gfap null mice did not parallel those of AxD [8]. Since then, many different GFAP mutations have been reported in AxD patients [9].