Fig. 3

K14-VEGFR3-Ig mice show delayed clearance of extracellular tau to the plasma after intra CNS injection. 4-6mo old WT (n = 6; 3 males, 3 females) and K14-VEGFR3-Ig mice (n = 5; 3 males, 2 females) were injected with anti-tau antibody HJ 8.5 to stabilize tau entering the plasma from the CNS to allow for its measurement. An hour later recombinant monomeric human tau was injected in the hippocampus and blood was collected at time points indicated. Plasma tau was measured using the ultrasensitive Simoa HD1-Analyzer platform. Though the overall difference between tau for the two mouse groups was not significant (p = 0.6766), the interaction between the two mouse groups over time was significant (p = 0.0191). Plasma tau peaks earlier in WT mice compared to K14-VEGFR3-Ig mice (24 vs 48 h). Amount of plasma tau is significantly higher in K14-VEGFR3-Ig mice at 48 h compared to WT mice (p = 0.0260), indicative of delayed clearance of tau due to impaired lymphatics. Data was analyzed by mixed effects linear model. Akaike’s AIC was used to evaluate 15 covariance structures to determine the best fit model for this analysis. Least square estimates of the differences between the two mouse groups at each time period were used to compare the trajectory of response over time