APPL1 and Alzheimer disease: With its expression in brain approximately doubled in Thy1-APPL1 mice, APPL1 recapitulated an aging-dependent onset of rab5 overactivation, early endosome swelling (Cataldo et al., 1997; Jiang et al., 2016; Kim et al., 2016; Mathews and Levy, 2019; Pensalfini et al., 2020), and loss of BFCNs, a phenotype invariably seen in AD brain and the various AD models that replicate AD-related early endosome dysfunction (Cataldo et al., 1997; Jiang et al., 2016; Kim et al., 2016; Pensalfini et al., 2020).