Although previous studies have revealed that β‐CTF elevation led to RAB5 hyperactivation and DS‐AD‐relevant degenerative phenotypes,16, 17, 40, 49 it was not clear whether physiologically relevant increases in RAB5 activity, as detected in DS brains, were directly responsible and how RAB5 hyperactivity led to ELN dysregulation. Here, ELN is linked to Alzheimer disease.