APP and Alzheimer disease: Additionally, screening at other targets of interest for AD treatment revealed that these hybrids can also inhibit in vitro butyrylcholinesterase (BChE), Aβ self-aggregation and BACE-1, the enzyme that catalyzes the first and rate-limiting step of the proteolytic cleavage of the amyloid precursor protein (APP) to Aβ, thereby expanding the in vitro multitarget profile of these compounds.