Designed to serve as multitarget-directed ligands for treating Alzheimer’s disease, these hybrids integrate (i) a tacrine moiety for cholinesterase’s inhibition, (ii) an 8-hydroxyquinoline or 8-aminoquinoline fragment for metal chelation, and (iii) a flexible linker to span both the CAS and PAS of AChE to prevent AChE-induced Aβ aggregation. This evidence concerns the gene ACHE and early-onset autosomal dominant Alzheimer disease.