APP and Alzheimer disease: In the past decade, many studies have uncovered a link between AD pathogenesis and Cu dysmetabolism (reviewed in [12]): AβPP/Aβ are Cu binding proteins with a potential role as natural Cu buffering proteins, and Cu2+ binding dramatically changes Aβ aggregation propensity, structure, and toxicity [13], with a plethora of effects spanning from reducing energy production in mitochondria to altering synaptic function and cognitive deterioration (reviewed in [12]), as revealed by preclinical models of chronic Cu exposure [14,15,16,17].