Lithium treatment reduced the dystrophic pathology associated to Abeta plaques. A) Representative western blot (n = 7 mice per group) and quantitative analysis of phosphorylated tau, determined using AT8 clone, of total proteins from PS1 control, PS1xAPP control and PS1xAPP lithium-treated mice. For quantification, the AT8 levels were referred to PS1 control group. The AT8 levels were significantly increased in PS1xAPP control mice (ANOVA F(2,18) = 22.66, p = 0.0001; Tukey p < 0.05) whereas PS1 control and PS1xAPP lithium displayed no differences. B) Representative AT8 positive dystrophies surrounding Abeta plaques from control (b1 and b2) or lithium treated (b3 and b4) PS1xAPP mice. C) Representative western blots and quantitative analysis of steady-state levels of LC3-II and ubiquitinated proteins in PS1 and PS1xAPP control and treated mice (n = 4 per genotype and treatment). A clear and significant accumulation of both LC3-II (ANOVA F(3,12) = 32.52, p = 0.001) and ubiquitinated proteins (ANOVA (F(3,12) = 63.67, p = 0.00001) was observed in PS1xAPP control mice. Lithium treatment reversed this pathology. The post-hoc analysis, using Tukey test, was indicated in the figure. D) Ubiquitin (d1 and d2) and LC3 (d3 and d4) immunolabeled hippocampal sections (counterstained with Congo red for Abeta plaques) of control and lithium treated PS1xAPP mice corroborated the accumulation of both markers, associated with dystrophic neurites surrounding amyloid plaques (d1 and d3) and the patent lithium reduction (d2 and d4) in the presence of ubiquitin and LC3 positive dystrophies. Inserts in d1-d4 showed higher magnification details of the dystrophies surrounding Abeta plaques. so, stratum oriens; sp, stratum pyramidale; sr, stratum radiatum. Scale bars: b1, b3 50 μm; b2, b4 100 μm; d1 to d4 200μm; inserts 25 μm.