MAPT and Alzheimer disease: The WT, AcK311,and AcK317 constructs demonstrated self-assembly, but only WT fibrilsformed PHF filaments under previously optimized conditions (confirmedthrough a cryo-EM structure that matched those isolated from AD brains).16,18 The self-assembly is facilitated by Tau–Tau binding, whichexhibits nanomolar affinities and is correlated with positional specificityand PTM identity.117 Interestingly, theAcK311 and P301S mutations accelerated heparin-induced aggregation,whereas AcK353, AcK369, AcK317, pS356, pS352, GlcNAcN359, and GlcNAcN359+ AcK353 inhibited aggregation.