Figure 3.
AD-tau is a more potent seed for tau aggregation in non-Tg mice. (A) Schematics showing injection sites in the dorsal hippocampus and overlying cortex indicated by red dots (Bregma −2.54 mm, 2 mm from midline, and −1.4 mm from skull [for the cortex] and −2.4 mm from skull [for the hippocampus]). (B) Differential induction of tau pathology recognized by AT8 (a monoclonal antibody specific for tau phosphorylated at S202/T205) in non-Tg mice at 3 mo p.i. of different tau fibrils. Amount of tau injected per mouse: 9 µg for Hep-T40 (four mice) and X-T40 fibrils (six mice); 8 µg for AD-tau (four mice). Contra, contralateral; Ctx, cortex; HP, hippocampus; Ipsi, ipsilateral. Bar, 100 µm. (C) AT8 immunostaining at 24 mo p.i. of Hep-T40 fibrils (9 µg/mouse; two mice). (D) AT8 immunostaining at 9 mo p.i. of X-T40 fibrils (9 µg/mouse; three mice). Considerable variability was found among injected animals, with the one mouse developing the most abundant pathology shown here. (C and D) Bars, 200 µm. (E) AT8 immunostaining at 3, 6, and 9 mo p.i. of AD-tau (8 µg/mouse; four mice per time point). Bar, 100 µm. (F) Quantification of percent area occupied by AT8-positive tau pathology developed in the ventral hippocampal hilus with 8 µg AD-tau injection (four mice per time point; each dot represents one mouse). One-way ANOVA was performed across different time points for ipsilateral and contralateral pathology separately. Significant differences were found for ipsilateral pathology, and Tukey’s multiple comparison test identified a significant difference between 3 and 9 mo p.i. *, P < 0.05. mpi, months p.i. (G) AD-tau inoculation (8 µg/mouse) did not lead to significant neuron loss in the ventral hippocampal hilus region as compared with mice injected with control (Ctrl) brain extracts. Data are shown as mean + SEM. One-way ANOVA found no significant differences among the groups. Data shown in this figure were obtained from injections performed all on 2–3-mo-old non-Tg mice (C57BL6 or C57BL6/C3H F1). Refer to Table S4 for the details of animals analyzed per group.