Fig. 2
From: Dural lymphatics regulate clearance of extracellular tau from the CNS
K14-VEGFR3-Ig mice retain significantly more tau in the brain following intra-CNS injection. a Panel showing distribution and gradual clearance of tau-cypate (as measured by longitudinal FMT) in a representative WT mouse from pre-injection through 168 h post-injection. Monomeric recombinant human tau was conjugated with the near-infrared fluorescent dye cypate and stereotactically injected in the hippocampus of WT and K14-VEGFR3-Ig mice. Mice were longitudinally imaged with FMT at the time-points indicated. The same injection and imaging timeline was followed for experiments involving clearance of HSA-cypate in WT and K14-VEGFR3-Ig mice b Significantly more tau is retained in the brain of K14-VEGFR3-Ig mice, indicating delayed clearance. 4–6 mo old WT (n = 9; 5 males, 4 females) and K14-VEGFR3-Ig mice (n = 6; 3 males, 3 females) were injected with tau-cypate in the hippocampus. They were imaged with FMT at 1, 2, 24, 48, 72 and 168 h post injection. The amount of fluorescence in the brain was quantified and normalized to values for the 1 h time point. A significantly higher amount of tau was retained in the K14-VEGFR3-Ig mice compared to WT mice at 48 h (85% vs 52% retention) and 72 h (52% vs 22% retention), following injection. Data was analyzed by a two-way ANOVA with a Bonferroni post-test. (** p-value < 0.01). c Significantly more HSA is retained in the brain of K14-VEGFR3-Ig mice, indicating delayed clearance. 4–6 mo old WT (n = 4; 1 male, 3 females) and K14-VEGFR3-Ig mice (n = 6; 4 males, 2 females) were injected with HSA-cypate in the hippocampus. They were imaged with FMT at 1, 2, 24, 48, 72 and 168 h post injection. The amount of fluorescence in the brain was quantified and normalized to values for the 1 h time point. A significantly higher amount of HSA was retained in the K14-VEGFR3-Ig mice compared to WT mice at 24 h (57% vs 29% retention) and 48 h (36% vs 15% retention) following injection. Data was analyzed by a two-way ANOVA with a Bonferroni post-test. (** p-value < 0.01, * p-value < 0.05). d Table summarizing half-life of tau and HSA in the CNS following their injection in both WT and K14-VEGFR3-Ig mice. The half-life of both proteins is longer in the K14-VEGFR3-Ig mice