APP and Alzheimer disease: Previous studies have shown that, in DS models, increased APP expression causes an increase in RAB5 activation (Xu et al., 2016), which creates enlarged early endosomes and may contribute to the AD commonly seen in DS patients (DS-AD) (Cataldo et al., 2003; Cattaneo and Calissano, 2012; Salehi et al., 2006; Xu et al., 2016).