APP and Alzheimer disease: Endosome anomalies are among the earliest disease-specific neuronal responses in AD and DS.63 In addition to βCTF of APP, other genetic factors have been reported to induce endosomal dysfunction in AD and DS, including synaptojanin164 and Vps34, a class III phosphoinositide 3-kinase,65 and possibly their relationships with rab5-dependent or -independent mechanisms deserve further investigation.