 The study examined the binding mechanism of a small molecule called GTP1 to the amyloid core of Alzheimer's disease tau protein. Using cryo-electron microscopy, they determined the structure of the tau protein bound to GTP1, which revealed a unique binding mode. The compound binds to a single site on the exposed cleft of each pitofilament in a stacked arrangement, mimicking the fibril symmetry of the Alzheimer's disease tau protein. Pi-pi aromatic interactions between the compound and the protein further support the high specificity and affinity of the binding. This binding mode provides important insights into how small molecules can be designed to target different amyloid folds found across neurodegenerative diseases. This article was authored by Gregory E. Morris, Matthew J. Chalkley, Sophia K. Tan, and others.