The role of copper in AD is gaining prominence with the discoveries that: (i) it is increased and/or mis-localized in the AD brain; (ii) enriched in extracellular plaques; (iii) deficient in Aβ plaque neighboring brain regions; and (iv) disease-linked proteins, APP, Aβ, tau, and BACE1, are copper-binding proteins with key roles in brain metal regulation (reviewed in Kozlowski et al., 2009; Hung et al., 2010). Here, APP is linked to Alzheimer disease.