Tauopathy-induced neurodegeneration is enhanced by amyloid deposition.
(a) Histochemistry of AChE fibers in the DG shows deafferentation-induced reorganization in the MML in 16-month-old rTgTauEC x APP/PS1 mice. Increased AChE staining in the MML is indicated by the arrow. (b) Comparing the ratio of optical densities between MML and IML demonstrates that the sprouting of AChE fibers is significant at 16 months of age in rTgTauEC x APP/PS1 mice compared to rTgTauEC, but no synaptic reorganization is evident in 10-month-old animals (10 and 16 month old animals, N = 3). (c,
d) High magnification views of the EC with FISH showing human tau mRNA (green) and immunostained for human tau protein (Tau13, red; scale bar = 50 μm). Transgene expression was robust in layer II of the EC in rTgTauEC mice, but nearly absent in rTgTauEC x APP/PS1 mice, despite strong labeling for human tau protein. (e) (Left) Quantification of FISH labeling reveals that rTgTauEC x APP/PS1 mice have a significant reduction in transgene expressing cells in the EC compared with rTgTauEC mice (rTgTauEC, N = 3; rTgTauEC x APP/PS1, N = 6). (Right) The EC of rTgTauEC x APP/PS1 mice also contained fewer cells that were positive for both human tau mRNA and tau protein. (f) Layer II of the EC of rTgTauEC x APP/PS1 mice contained significantly fewer cells than rTgTauEC mice. Values represent mean ± s.e.m; *P < 0.05, ***P < 0.001.