Fig. 1: Overview of the tau epitopes recognized by the anti-tau VHHs used in this study and schematic representation of the tau neuronal uptake assays.
From: Inhibition of tau neuronal internalization using anti-tau single domain antibodies
a Schematic representation of the tau epitopes recognized by each anti-tau VHH. VHH B1-1 binds to the tau proline-rich domain (PRD). VHH C3-2 binds to the amino-acid sequence located between the PRD and the R1 repeat of the tau microtubule-binding domain (MTBD). VHH A31 binds to the PHF6* region within the R2 repeat (Supplementary Fig. 1). VHH Z70mut1 binds to the PHF6 region within the R3 repeat. VHH A5-2 binds to the R4 repeat. VHH F8-2, E2-2, and H3-2 bind to the C-terminal domain (C-ter) of tau (Supplementary Fig. 2). The epitopes were determined by 2D NMR interaction mapping experiments, as previously described28,29,30. b Schematic representation of the tau cellular uptake assay. Recombinant monomeric (tau_M) or fibrils of tau1N4R (tau_F) labeled with fluorescent dyes (Alexa546 and Atto565, respectively) and VHHs were co-incubated for 30 min at room temperature (RT). Tau-VHHs complexes were then incubated with primary neurons for 1 h at 37 °C. Finally, cells were washed and analyzed by confocal microscopy or lysed and transferred to a 96-well plate for fluorescence imaging. Created in BioRender. Tautou, M. (2025) https://BioRender.com/a27l880.
