FIGURE 4.

Immunohistochemical analysis of PrPSc deposition and association with human tau in transgenic mouse brains. All brain tissues from scrapie-infected mice were obtained at the time of clinical disease. (A-G) Representative sections from a RML scrapie-infected huTau+ mouse and (H-J) 22L scrapie-infected huTau+ mouse are shown. (A) Whole brain sagittal section demonstrating widespread PrPSc staining with D13 (red) and boxes depicting areas enlarged in D-F. (B, C) PrPSc plaque stained with D13 and Thioflavin S respectively. (D-J) Dual staining of PrPSc with D13 (red) and P-tau using anti-P-tau antibody CP13 (brown). A clear association of P-tau aggregates can be seen around PrPSc plaques (yellow arrows) in several regions of the brain including (D) frontal dorsal cortex, (E) hypothalamus, (F,G,H) colliculus, and (I,J) dorsal cortex. Non-amyloid PrPSc (black arrowheads) rarely had P-tau staining nearby. Scrapie-associated vacuoles (blue arrowheads) could be seen in some brain regions. (K) Minimal P-tau staining by CP13 in cortex of 22L scrapie-infected huTau− mouse. (L) Absence of D13 and CP13 staining in an uninfected huTau+ mouse. (M) PrPSc amyloid plaque from a huTau+ 22L scrapie-infected mouse stained with CP13. Note, without D13 staining the localization of P-tau in ring-like structures (pink arrows) is more obvious. The scale bar in each panel is 50 µm.