PSEN1 and Alzheimer disease: β-CTF-dependent (but Aβ-independent) overactivation of Rab5, a small GTPase associated with early endosome, has been shown to cause endosomal abnormalities in neurons from AD patients (Kim et al., 2016), induced pluripotent stem cells (iPSCs) derived from AD patients (Israel et al., 2012) and CRISPR/Cas9-generated iPSC lines carrying FAD mutations (Kwart et al., 2019).