Alexander disease: A slowly progressive and ultimately fatal brain disorder that most commonly occurs in children. The infantile form of the disease is characterized by megalencephaly (an abnormally large head), seizures, spasticity and developmental retardation. It leads to death usually within the first decade. Patients with the juvenile and adult forms of Alexander disease typically experience ataxia and spasticity and a more slowly progressive course. The classic hallmark of all forms of Alexander disease is the presence of Rosenthal fibers, abnormal inclusions in astrocytes that contain the intermediate filament protein GFAP. Mutations in the gene for GFAP (glial fibrillary acidic protein) cause Alexander disease, the first known example of a primary genetic disorder of astrocytes, one of the major cell types in the vertebrate CNS . The disease was first described by W. Stewart Alexander, a New Zealand pathologist , in 1949.

Rosenthal fibers are homogeneous masses which form elongated tapered rods scattered throughout the cortex and white matter of the brain. Rosenthal fibers are located in the astrocytes. Demyelination (loss of myelin , the insulation around nerves) is also a prominent feature of the disease. Alexander disease is classified as one of the leukodystrophies , the diseases of the white matter of the brain.

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