Applying this same approach to the M1-receptor, a receptor widely considered as a validated target for improving memory loss and promising disease-modification in AD (7), our previous studies have established that activating ligands that maintain receptor phosphorylation/arrestin-dependent signaling may deliver clinically relevant efficacy, such as mediating procognitive effects,, while minimizing cholinergic adverse responses (17). Here, SAG is linked to Alzheimer disease.