APP and Alzheimer disease: More importantly, Alić et al recently have found that BACE2 was a dose-sensitive AD-suppressor gene in human brains and hPSC-derived BOs, thereby potentially explaining the dementia delay in ~30% of people with Down Syndrome [31], which is consistent with our conclusion that dysregulation of BACE2-mediated APP cleavage may represent a pathological mechanism for AD.