APP-βCTF levels are elevated in human AD brain (Pera et al., 2013; Kim et al., 2016) and in AD models where they contribute directly to early endosome dysfunction, disrupted endosomal trafficking, and neuronal loss (Jiang et al., 2010, 2016, 2019; Lauritzen et al., 2016; Bourgeois et al., 2018; Colacurcio et al., 2018). Here, APP is linked to Alzheimer disease.