Recently, by crossing a trisomic Hsa21 mouse model (Tc1), which has an extra copy of 75% Hsa21 genes but lacks an additional functional copy of APP, with an APP-amyloid deposition mouse model (J20-tgAPP) [12–14], we found that three copies of Hsa21 genes other than APP exacerbate Aβ deposition and cognitive deficits [15], indicating that other Hsa21 genes may also play important roles in the pathogenesis of AD-DS. Here, APP is linked to Cognitive impairment.