Fig. 5

Phospho-tau accumulation in DKI mice is reduced by Prnp knockout. A Representative images of AT8 (red) staining in the medial cortex of 10-month-old old WT, Prnp^−/−, DKI and DKI; Prnp^−/− mice. Gray is DAPI signal, and AT8 inclusions are indicated by yellow arrows in the upper four panels with scale bar = 50 μm. The lower two panels show the AT8 signal only in gray scale at higher magnification with scale bar = 12.5 µm. B Quantification of AT8 immunoreactive area in retrosplenial cortex demonstrates a significant increase in phospho-tau accumulation in DKI mice compared to WT. There is a significant decrease in DKI; Prnp^−/− mice relative to DKI. Data are graphed as mean ± SEM, analyzed by ordinary one-way ANOVA with Tukey’s multiple comparisons test, **P < 0.01,****P < 0.0001, n = 9 for WT, n = 11 for Prnp^−/−, n = 9 for DKI, and n = 11 for DKI; Prnp^−/−. C Representative images of pThr217 (green) staining in the CA1 of hippocampus of 10-month-old WT, Prnp^−/−, DKI and DKI; Prnp^−/− mice. Gray is DAPI signal, and pThr217 inclusions are indicated by arrows in the upper four panels with scale bar = 50 μm. The lower two panels show the pThr217 signal only in gray scale at higher magnification with scale bar = 12.5 µm. D Quantification of pThr217 immunoreactive area in CA1 demonstrates a significant increase in phospho-tau accumulation in DKI mice compared to WT. The DKI; Prnp^−/− samples show a significant decrease relative to DKI. Data are graphed as mean ± SEM, analyzed by ordinary one-way ANOVA with Dunnett’s multiple comparisons test, *P < 0.05, **P < 0.01,****P < 0.0001, n = 17 for WT, n = 15 for Prnp^−/−, n = 17 for DKI, and n = 18 for DKI; Prnp^−/−. E Immunoblot image of cortical brain lysates stained for AT8 from 20-month-old WT, Prnp^−/−, DKI and DKI; Prnp^−/− mice. A cropped region of the blot with migration of appropriate Mol Wt markers is shown at left. F Quantification of AT8 antibody immunoreactive protein levels by densitometric analysis. The level of Tau phosphorylated at S202/T205 (AT8) is significantly greater in DKI mice compared to WT or Prnp^−/−. The DKI; Prnp^−/− AT8 level is less than that from DKI. Data are graphed as mean ± SEM, analyzed by ordinary one-way ANOVA with Dunnett’s multiple comparisons test, *P < 0.05, **P < 0.01, n = 10 for WT, n = 10 for Prnp^−/−, n = 10 for DKI, and n = 9 for DKI; Prnp^−/−