Summary

Alexander disease is an extremely rare, usually progressive and fatal, neurological disorder. Initially it was detected most often during infancy or early childhood, but as better diagnostic tools have become available has been found to occur with similar frequency at all stages of life. Alexander disease has historically been included among the leukodystrophies--diseases of the white matter of the brain. These diseases affect the fatty material (myelin) that forms an insulating wrapping (sheath) around certain nerve fibers (axons). Myelin enables the efficient transmission of nerve impulses and provides the "whitish" appearance of the so-called white matter of the brain. There is a marked deficit in myelin formation in most early onset patients with Alexander disease, and sometimes in later onset patients, particularly in the front (frontal lobes) of the brain's two hemispheres (cerebrum). However, white matter defects are sometimes not observed in later onset individuals. Instead, the unifying feature among all Alexander disease patients is the presence of abnormal protein aggregates known as "Rosenthal fibers" throughout certain regions of the brain and spinal cord (central nervous system [CNS]). These aggregates occur inside astrocytes, a common cell type in the CNS that helps maintain a normal CNS environment. Accordingly, it is more appropriate to consider Alexander disease a disease of astrocytes (an astrogliopathy) than a white matter disease (leukodystrophy).