Beyond the brain: widespread pathology in Huntington's disease

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a polyglutamine stretch in the huntingtin protein. Today, more than 15 years after the genetic defect underlying HD was discovered, the pathogenesis is still not well understood and there is no adequate treatment. Research into this disorder has conventionally focused on neurological symptoms and brain pathology, particularly neurodegeneration in the basal ganglia and cerebral cortex. Mutant huntingtin is, however, ubiquitously expressed throughout the body. Indeed, contrary to earlier thinking, HD is associated with abnormalities in peripheral tissues. These abnormal changes are not all secondary to brain dysfunction, but most seem to be directly caused by expression of mutant huntingtin in peripheral tissues. In this article, we highlight this emerging field of research and how it might affect our understanding of the pathogenesis of this disease, the development of novel biomarkers of disease progression, and the identification of new potential treatments.