Adult-onset autosomal dominant leukodystrophy (ADLD) was first described for a large kindred with a progressive and fatal neurological white matter disorder in an American-Irish family (Eldridge et al., 1984). Subsequently, ADLD has been reported in many other ethnic groups including Japanese, Swedish, French, Italian, and French Canadian (Asahara et al., 1996; Marklund et al., 2006; Melberg et al., 2006; Meijer et al., 2008; Brussino et al., 2009, 2010). Clinically, ADLD is a progressive degenerative neurological disorder with pyramidal, cerebellar, and autonomic disturbances (Eldridge et al., 1984; Coffeen et al., 2000; Marklund et al., 2006; Melberg et al., 2006). The symptoms begin between the forth and sixth decades (mean age of 40 years) of life with early presentation of autonomic symptoms, including bowel/bladder dysfunction, impotence in males, and orthostatic hypotension (Schwankhaus et al., 1988; Coffeen et al., 2000). Autonomic symptoms precede cerebellar signs (ataxia, dysmetria, nystagmus, and action tremors) and pyramidal abnormalities (spasticity and weakness of both upper and lower extremities). Mild cognitive, visual, and auditory abnormalities are also present in some cases. The peripheral nervous system is spared (Schwankhaus et al., 1994). Upper motor neuron signs such as spastic paralysis, posterior column dysfunction, and extensor plantar responses are also common phenotypic characteristics (Coffeen et al., 2000). In addition to the clinical history and physical examination, magnetic resonance imaging (MRI) is the best method to diagnose ADLD. The MRI scans display diffuse, confluent and symmetric white matter involvement starting in the frontoparietal region, extending to the brainstem and cerebellar white matter (Fig. 1)(Bergui et al., 1997; Coffeen et al., 2000; Melberg et al., 2006). Periventricular white matter appears less affected than the adjacent white matter (Melberg et al., 2006). The diameter of the medulla oblongata is reduced in the coronal plane and the corpus callosum is atrophic (Schwankhaus et al., 1988; Melberg et al., 2006). Although spinal cord involvement has been reported in some cases (Sundblom et al., 2009), white matter changes are most significant in the brain. Neuropathological findings revealed white matter abnormalities in the frontoparietal and cerebellar white matter, whereas the cortex and subcortical U fiber showed no significant pathology in symptomatic ADLD patients (Schwankhaus et al., 1988; Coffeen et al., 2000; Melberg et al., 2006). Light microscopy showed vacuolated white matter with no significant loss of oligodendroglia accompanied by an absence of inflammatory changes and reactive astrocytosis (Coffeen et al., 2000; Melberg et al., 2006). Sparse astrocytes with intense reaction products (insulin-like growth factor-1 and vimentin) are accompanied by abnormally beaded or