Fig. 4: Soluble tau aggregate accumulation in brain microvasculature of P301S(PS19) mice is associated with profound deficits in endothelium-dependent vasodilation.

A Impaired endothelium-dependent cerebral blood flow (CBF) responses in male and female P301S(PS19) mice in response to topical acetylcholine (ACh) stimulation as compared to WT animals worsen with age (F(3,125) = 53.04, ANOVA, p < 0.0001. * indicates Tukey’s q(126) = 3.80, ** indicates Tukey’s q(126) = 4.66, p < 0.007; **** indicates Tukey’s q(126) = 6.16, p < 0.0001). The bracket highlights significant worsening of endothelial dysfunction with age in P301S(PS19) mice, ** Tukey’s q(126) = 4.61, WT 4 months, n = 6; PS19 4 months, n = 6; WT 8 months, n = 7; PS19 8 months, n = 6 mice. Four-month-old animals were males. Eight-month-old animals were males and females. Data are means ± SEM, plotted against ACh-induced vasodilation in C57BL/6 J mice, that serve as reference and were not included in the analysis. B, C Accumulation of tau in brain microvasculature isolated from 8-month-old P301S(PS19) mice. B Representative electropherograms from capillary electrophoresis immunoassays showing increased tau in brain vasculature isolated from 8-month-old, male and female P301S(PS19) mice. C Quantitative analyses of data in (C) (Two-sided Student’s t-test t(5.064) = 3.116, *, p = 0.026. Control, n = 6; PS19, n = 6 mice). Data are representative images and means ± SEM. For post-hoc analyses, lack of a specific P value in the legend reflects the information reported by GraphPad Prism Version 9.4.0.