Fig. 1.

Loss of tau in TgA53T mice delays disease onset and progression following αS PFF inoculation. a Schematic of study paradigm, including genotypic groups, collection time points, behavior, and disease staging analysis. b, c Kaplan–Meier plots of all groups showing disease onset (onset of motor abnormalities) (b; P = 0.0122; Log-rank (Mantel Cox) test) and time to reach end stage (hind limb paralysis) (c; P = 0.0022; Log-rank (Mantel Cox) test). Both onset and time to end stage were delayed in TgA53T mice lacking tau (TgA53T/mTau^−/−). d Average duration from disease onset to end stage was also significantly extended with loss of tau (P = 0.0247; t-test). e Performance on rotarod at 70 dpi showed that TgA53T mice exhibited decreased latency to fall compared to TgA53T/mTau^−/− subjects. One-way ANOVA with Tukey’s post-hoc analysis; Day 3: F_(3,18) = 4.925, P = 0.0114; Day 4: F_(3,18) = 3.150, P = 0.0505. f, g TgA53T mice required more time to descend the pole (f) and complete (turn and descend) the pole test (g) compared to nTg and mTau^−/− controls, while performance of the TgA53T/mTau^−/− mice was not significantly different from all other groups, indicating that loss of tau expression results in partial protection from impaired performance. Abbreviations: preformed fibril, PFF; days post inoculation, dpi; immunohistochemistry, IHC; biochemistry, BC; seconds, s. One-way ANOVA with Tukey’s post-hoc analysis; time to descend: F_(3,20) = 4.186, P = 0.0188; time to perform: F_(3,20) = 4.220; P = 0.0182. n = 8–11 animals/genotype (survival), n = 5–7 animals/genotype (behavior). *P < 0.05 and **P < 0.01; error bars represent mean ± SEM