Disease relevance of Alexander Disease

• The CT scans obtained from these patients with proved Canavan's disease appeared to be quite characteristic in differentiating this disorder from Alexander's disease and adrenoleukodystrophy (Schilder's disease) [1].
• On the other hand, over-expression can be lethal, and led to the discovery that GFAP coding mutations are responsible for most cases of Alexander disease, a devastating neurodegenerative disorder [2].
• Mutations in human GFAP have been associated with a severe childhood brain disorder called Alexander disease [3].

High impact information on Alexander Disease

• These results suggested that a primary alteration in GFAP may be responsible for Alexander disease [4].
• Infants with Alexander disease develop a leukoencephalopathy with macrocephaly, seizures and psychomotor retardation, leading to death usually within the first decade; patients with juvenile or adult forms typically experience ataxia, bulbar signs and spasticity, and a more slowly progressive course [4].
• Alpha B-crystallin is expressed in non-lenticular tissues and accumulates in Alexander's disease brain [5].
• These results confirm that GFAP mutations are a reliable molecular marker for the diagnosis of infantile Alexander disease, and they also form a basis for the recommendation of GFAP analysis for prenatal diagnosis to detect potential cases of germinal mosaicism [6].
• Overexpression and abnormal modification of the stress proteins alpha B-crystallin and HSP27 in Alexander disease [7].

Chemical compound and disease context of Alexander Disease

• In all the cases of Alexander's disease examined, strong immunolabeling of RF by the antibodies to 4-hydroxy-2-nonenal pyrrole adducts were noted [8].
• In this study, we immunohistochemically examined three cases of Alexander's disease using antibodies to a lysine-derived pyrrole modification arising from 4-hydroxy-2-nonenal, a highly cytotoxic reactive aldehyde produced by lipid peroxidation [8].
• alpha B-Crystallin is a major protein component of Rosenthal fibers, which massively accumulate in the brains of patients suffering from Alexander's disease [9].
• In contrast, the larger, pathological Rosenthal fibers characteristic of Alexander's disease were labeled after both etching procedures, but labeling was enhanced after ethoxide etching [10].
• Capillaries in brain biopsies obtained from patients with globoid cell leukodystrophy (GLD), adreno-leukodystrophy (ALD), Canavan's disease (spongy degeneration) and Alexander's disease were examined ultrastructurally and morphometrically [11].

Biological context of Alexander Disease

• Sequence analysis of DNA samples from patients representing different Alexander disease phenotypes revealed that most cases are associated with non-conservative mutations in the coding region of GFAP [4].
• Here we report that a 10-year-old Japanese patient who showed clinical signs of Alexander disease is heterozygous for a C to T transition in which predicts a novel A244V amino acid substitution in the conserved 2A alpha-helix domain of GFAP [12].
• Since the first report by Brenner et al. of mutations in the glial fibrillary acidic protein (GFAP) gene in patients with Alexander disease, several molecular genetic studies have been performed in different ethnic groups [13].

Gene context of Alexander Disease

• Alexander-disease mutation of GFAP causes filament disorganization and decreased solubility of GFAP [14].
• Plectin regulates the organization of glial fibrillary acidic protein in Alexander disease [15].
• The increased amounts of stress proteins and GFAP results in the formation of Rosenthal fibers, similar to those found in Alexander's disease [16].
• GFAP levels in the CSF were highly elevated in three genetically confirmed cases of Alexander disease clinically conforming with infantile, early and late juvenile forms [17].
• Alexander disease: Alzheimer disease of the developing brain [18]?

References