Some deletions and rearrangements occurred during construction of the model, and, as a result, Tc1 mice are functionally trisomic for ~75% of protein coding genes (Choong et al., 2015; Gribble et al., 2013), but, importantly, not APP. Therefore Tc1 mice are a good model in which to test the contribution of Hsa21 genes other than APP to AD on a DS background. Here, APP is linked to Alzheimer disease.