The shape of water defines the hotspot that starts tau aggregation in dementia
In a new study published in PNAS with collaborators at UC Santa Barbara, Chung-Ta Han, Karen Tsay and Songi Han found that aggregation-prone tau has a single dominant hotspot that binds the matching site on the end of a growing fibril, after which the incoming tau misfolds to match that shape. This hotspot sits in a hydrophobic region capped by a dynamic, ice-like layer of water, and releasing that water when two hotspots meet is what locks the tau molecules together in perfect register. When the team blocked the hotspot with a chemical tag, fibril growth stopped, which points to a new target for therapeutics and diagnostics and a path toward synthetic tau fibrils that mimic disease.
Read the paper: https://www.pnas.org/doi/10.1073/pnas.2611158123
Northwestern Now Story: https://news.northwestern.edu/stories/2026/10/the-shape-of-water-defines-the-hotspot-that-starts-protein-aggregation-in-dementia