Cocaine- and amphetamine-regulated transcript is increased in Huntington disease.

Weight loss and anxiety frequently occur in individuals with Huntington's disease (HD) but the underlying mechanisms are not well-understood. Peptides produced in the hypothalamus are involved in regulating energy homeostasis and emotion. Recent data suggest that changes in neuropeptide levels may be reflected in the cerebrospinal fluid (CSF), and could therefore serve as biomarkers for HD. Cocaine- and amphetamine-regulated transcript (CART) is a neuropetide expressed in several brain regions such as the hypothalamus, amygdala, and hippocampus. CART has been shown to increase anxiety and reduce food intake in rodents by as yet unknown mechanisms. Individuals with a CART mutation exhibit increased anxiety. In cross-sectional CSF samples from HD patients (n = 39), we found that levels of CART peptide were significantly increased by 23% compared to control subjects (n = 28). Increased CART levels in HD therefore hold promise as a biomarker as well as a potential pathogenic mediator of symptoms.