We have developed several classes of multitargetlinked hybridsthat combine huprine or 6-chlorotacrine with polyphenol moieties,such as capsaicin,54 the chroman derivativeCR-6,41 and shogaols,45 with the tau aggregation inhibitor rhein33 and/or with ligands of the aforementioned secondary bindingpocket of BACE-142 to simultaneously copewith the central cholinergic deficit and the oxidative stress or taupathologies characteristic of AD (Figure 16). Here, MAPT is linked to Alzheimer disease.