When the AChE inhibitor tacrine, a drug used in the past to treat Alzheimer's disease, was perfused on living cells expressing CLASH-AChE/HCA, tacrine displaced the secondary ligand from AChE, allowing the benzenesulfonamide to bind HCA and leading to high FRET efficiency of the sensor (Fig. 4c-d). This evidence concerns the gene ACHE and early-onset autosomal dominant Alzheimer disease.