Fig. 3.

ADT40P1 is pathogenic in vivo. a IHC of 6-month-old 5xFAD mouse brain sections. Mice injected with the same concentration of tau for 100% seeds control (100% AD-tau), 10% seeds control (10% AD-tau + 90% T40, no agitation) and ADT40P1. Mice were killed at 1-month post-injection and brains were probed with the AT8 antibody for phospho-tau; upper panel scale bar = 200 µm; low panel scale bar = 100 µm; arrow heads show amyloid-beta plaque adjacent to neuritic plaque tau pathology. b X34 staining of sections adjacent to those in a; arrow heads show neuritic plaque tau pathology associated amyloid-beta plaques in stained by the amyloid histochemical dye X34; scale bar = 200 µm. c Quantification of AT8 tau pathology from a; *P < 0.05 10% seeds vs ADT40P1, **P < 0.01 ADT40P1 vs 100% seeds, ***P < 0.001 100% seeds vs 10% seeds, one-way ANOVA followed by Tukey post hoc test; n = 6 for 10% seeds and ADT40P1 groups, n = 4 for 100% seeds control. d Quantification of X34-positive amyloid-beta plaques from b; n.s. nonsignificant, one-way ANOVA followed by Tukey post hoc test; n = 6 for 10% seeds and ADT40P1 groups, n = 4 for 100% seeds control. e Immunofluorescence staining (IF) of neuritic plaque tau pathology visualized using phosphor-tau (AT100/CP13) and mouse tau antibodies (R2295M) together with anti-amyloid beta (1–42) H31L21 antibody and X34 dye; scale bar = 50 µm. f Heat map of AT8-positive pathology distribution from a; 100% AD seeds vs ADT40P1. Gray represents no pathology. Low to high tau pathology score is represented as a gradient of green to red hues