BACE1 and Alzheimer disease: In the past decades, anti-AD drug discovery has mainly focusedon the Aβ cascade hypothesis although with disappointing results,as demonstrated by the recent failures of anti-Aβ antibody solanezumaband BACE-1 inhibitor verubecestat.127 However,other target-directed approaches have shown unsatisfactory results.128 There are many reasons for these failures.As previously discussed, a central point is represented by the factthat AD is a multifactorial disease driven by dysregulation of differentbut interconnected biochemical pathways.