Among its various neuronal signaling functions (Lin et al., 2006; Deepa and Dong, 2009; Lee et al., 2011; Hupalowska et al., 2012), APPL1 acts as a molecular link between APP-βCTF and rab5 (Kim et al., 2016), a critical crossroads for pathways that converge on the early endosome during AD pathobiology. Here, APP is linked to Alzheimer disease.