APP and Alzheimer disease: To this end, we used the Ts65Dn mouse model of DS, which bears a segmental trisomy for MMU16 (syntenic region to HSA21) from Mrpl39 to Zfp295 covering APP and DYRK1A, and shows predictive validity with DS (reviewed in Dierssen, 2012) including AD-like cholinergic neuronal loss and age-associated cognitive decline (Holtzman et al., 1996; Seo and Isacson, 2005; Contestabile et al., 2006).