Andrew P Longhini, Austin DuBose, Samuel Lobo, Vishnu Vijayan, Yeran Bai, Erica Keane Rivera, Julia Sala-Jarque, Arina Nikitina, Daniel C Carrettiero, Matthew T Unger, Olivia R Sclafani, Valerie Fu, Emily R Beckett, Michael Vigers, Luc Buée, Isabelle Landrieu, Scott Shell, Joan E Shea, Songi Han, Kenneth S Kosik
Prion-like spread of disease-specific tau conformers is a hallmark of all tauopathies. A 19-residue probe peptide containing a P301L mutation and spanning the R2/R3 splice junction of tau folds and stacks into seeding-competent fibrils and induces aggregation of 4R, but not 3R tau. These tau peptide fibrils propagate aggregated intracellular tau over multiple generations, have a high β-sheet content, a colocalized lipid signal, and adopt a well-defined U-shaped fold found in 4R tauopathy brain-derived fibrils...
April 9, 2024: Proceedings of the National Academy of Sciences of the United States of America