Fig. 6: Removal of soluble tau aggregates from the brain ameliorates brain microvascular deficits in 12-month-old male and female P301S(PS19) mice. | Nature Communications

Fig. 6: Removal of soluble tau aggregates from the brain ameliorates brain microvascular deficits in 12-month-old male and female P301S(PS19) mice.

From: Soluble pathogenic tau enters brain vascular endothelial cells and drives cellular senescence and brain microvascular dysfunction in a mouse model of tauopathy

Fig. 6

A, B Treatment with TOMA ameliorates profound deficits in endothelium-dependent vascular responses in somatosensory cortex of P301S(PS19) mice, restoring vascular responses to levels comparable to those of 4-month-old animals. A ACh-stimulated vascular responses; B Quantitative analyses of data at 25 min in A. Interaction of time and treatment group by 2WRM ANOVA, F(10,50) = 4.91, p < 0.0001; difference from WT by Holm-Sidak’s post hoc indicated as *, t(60) = 2.86, p = 0.02; **, t(60)=3.33, p = 0.003; ***, t(60) = 4.04, p = 0.0005; ****, t(60) = 5.31, p < 0.0001; # indicates difference from PS19 + TOMA, for all #s, t(60)>2.34, p < 0.046 by Holm-Sidak’s post hoc. WT, n = 4; PS19, n = 4; PS19 + TOMA, n = 5 mice. Data from 4-month-old WT and P301S(PS19) groups (Fig. 1) serve as reference and were not included in the analysis. C, D Treatment with TOMA reduces levels of soluble tau aggregates (tau oligomers) in brains of P301S(PS19) mice. C Representative immunoblots of cortical lysates of P301S(PS19) mice treated with isotype-matched IgG (PS19) or TOMA (PS19 + TOMA); D, Quantitative analyses of data in (C) (F (2, 19) = 6.807, ANOVA, p = 0.0081. WT vs. PS19, **, p < 0.01; PS19 vs PS19 + TOMA, *, p < 0.05 by Tukey’s post hoc test. WT, n = 8; PS19, n = 7; PS19 + TOMA, n = 7 mice). E, F TOMA treatment reduces levels of vascular tau in brains of P301S(PS19) mice. E Representative images (100X) of tau immunoreactivity (green) associated with lectin-reactive cortical brain vasculature (red), counterstained with DAPI (blue) staining. Scale bar is 50 µm. F Quantitative analyses of data in (E) (H = 6.839, Kruskal–Wallis test, *, p = 0.026. WT vs. PS19, *p < 0.05 from Dunn’s. n.s., no significant difference between experimental means for WT vs PS19 + TOMA. WT, n = 5; PS19, n = 7; PS9 + TOMA, n = 8 mice per group). G, H Cortical brain vascular density in P301S(PS19) mice is unchanged by tauopathy or by TOMA immunotherapy. G Representative images (40X) of lectin-reactive cortical brain vasculature (red) of P301S(PS19) animals treated with TOMA (PS19 + TOMA) or isotype-matched IgG (PS19). Scale bar is 250 µm. H Quantitative analyses of data in (G) (H = 1.787, Kruskal–Wallis, p = 0.426. WT, n = 5; PS19, n = 8; PS19, n = 7 mice). Data are representative images and means ± SEM. For post-hoc analyses, a lack of a specific P value in the legend reflects the information reported by GraphPad Prism Version 9.4.0.

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