APP and Alzheimer disease: Lowered Aβ levels can also be achievedby inhibition of β-secretase(BACE1) and γ-secretases that are responsible for the so-calledamyloidogenic pathway of amyloid precursor protein (APP) breakdown.BACE1 inhibitors entered clinical trials and were tested in patientsat early and mild-to-moderate stages of AD with fully developed Aβpathology.12,13 Elenbecestat (E-2609, Eisai),14 verubecestat (MK-8931, Merck),15 and atabecestat (JNJ-911, Janssen)16 reached phase III clinical trials but failed due to lack of clinicalefficacy or observed toxicity.12,17,18