ACHE and Alzheimer disease: Indeed, a large part of the MTDLs strategiesadopted in AD are based on the combined inhibition of AChE and anotherAD-relevant target.25 However, since Cavalli,Bolognesi, and co-workers brought to light the first-in-class dualβ-secretase (BACE-1)/glycogen synthase kinase 3β (GSK-3β)inhibitors, the interest in developing MTDLs acting as GSK-3βinhibitors has increased.26,27 Undoubtedly, this isalso a consequence of the growing importance of the tau hypothesisand the prominent role assumed by GSK-3β in this context.28