APP and Alzheimer disease: Cu2+ complexes of bis-thiosemicarbazones, especially Cu(gtsm), have been demonstrated to increase intracellular copper levels and decrease secreted Aβ levels in APP-CHO cells.129 APP/PS1 transgenic AD mice treated with Cu(gtsm) showed lower abundance of Aβ trimers and phosphorylated tau.130 The underlying mechanism might be that Cu2+ ions binding to APP promote the non-amyloidogenic APP processing pathway and therefore decrease the production of Aβ.