Fig. 2. Heparin-free tau fibrils have an extended core and an immobile N-terminal antibody-binding epitope.

a Cartoon representation of the rigid core and dynamic (termed fuzzy) coat of tau fibrils. b SDS-PAGE gel of trypsin-digested tau fibrils formed in the absence or presence of heparin. The trypsin band is indicated. The result was reproducible for three independently performed experiments. c Number of peptides detected from the enzymatic digestion of the tau bands observed in SDS-PAGE in (a). The position of lysine and arginine residues of 2N4R tau are marked with purple and green dots, respectively. d Superposition of ¹H-¹⁵N INEPT spectra of 2N4R tau fibrils aggregated in the absence (orange) and presence (black) of heparin. e Intensity ratio plot of 2N4R tau fibrils aggregated in the absence (orange) and presence (black) of heparin. The intensity ratio was calculated by dividing the signal intensity of each residue in the fibril state by the monomeric state. The error of the intensity ratio for each residue was calculated from the signal-to-noise ratio of the cross peaks in the spectra. The rigid cross-ß-sheet core of the tau fibril extracted from a CBD patient brain (PDB code: 6TJO) is marked in light blue. The two discontinuous epitopes (residues 1–18 and residues 313–322) of antibodies that specifically detect pathological tau¹⁸ are marked by red boxes.