Small-molecule Tau aggregation inhibitors are under investigation as potential therapeutic
agents against Alzheimer disease. Many such inhibitors have been identified in vitro, but
their potency-driving features, and their molecular targets in the Tau aggregation pathway,
have resisted identification. Previously we proposed ligand polarizability, a measure of
electron delocalization, as a candidate descriptor of inhibitor potency. Here we tested this
hypothesis by correlating the ground state polarizabilities of cyanine, phenothiazine, and …