Whether enlarged or clustered, the significant upregulation in the levels of active Rab5 (GTP-loaded Rab5), which drives endosome fusion, support the importance of changes in early endosomes in DS and AD-DS, as well as in non-DS AD (Xu et al., 2016; Chen X. Q. et al., 2021). Here, RAB5A is linked to Alzheimer disease.