Abnormally high concentrations of Cu have been found in the striatum in patients with HD and in mouse models of HD.135,136 Moreover, several reports have suggested that an accumulation of Cu promotes aggregation of the HTT protein and interacts with histidine residues at the N-terminus of the protein.136 In vitro studies have shown that Cu binds to HTT proteins with 17–68 glutamine residues, whereas neither Fe nor Zn exhibits binding affinity. Here, HTT is linked to Huntington disease.