Table 1.
APP/Aβ mutants used in this study.
Fig 1.
Reduction in dendritic spine density in hippocampal slices from Tg2576 and arcAβ- but not E22ΔAβ transgenic mice.
A: Representative confocal images of dendritic segments of hippocampal slices from Tg2576, arcAβ- and E22ΔAβ transgenic mice and the respective non-transgenic littermates. B: Spine counts per μm dendrite. Spine density was reduced in cultures from Tg2576 tg mice and arcAβ tg mice but not in E22ΔAβ tg mice. Treatment with 0.5 μM DAPT abolished spine reduction in arcAβ tg slices. n = 10–12; Data are means ± SD. Statistical significance was assessed by one-way ANOVA with Tukey's multiple comparison test (***p<0.001). Scale bar: 5 μm.
Fig 2.
Reduction in dendritic spine density in hippocampal slices treated with recombinant wt and E22G Aβ but not E22Δ Aβ.
A: Representative confocal images of dendritic segments of wild-type mice treated with 1 μM recombinant Aβ for 7 days. B: Spine counts per μm dendrite. Spine density was reduced after treatment with wt Aβ42 and E22G Aβ42 but not E22Δ Aβ42. Incubation with wt Aβ40 and E22G Aβ40 caused a mild reduction in spine numbers, whereas no effect was observed for E22Δ Aβ40. n = 10–15; Data are means ± SD. Statistical significance was assessed by one-way ANOVA with Tukey's multiple comparison test (*p<0.05; ***p<0.001). Scale bar: 5 μm.
Fig 3.
Induction of tau phosphorylation and tau-dependent cell death by wt and E22G Aβ but not E22Δ Aβ.
A: Cytotoxicity in human tau expressing slices from Tg2576, arcAβ- and E22ΔAβ tg mice and the respective non-transgenic littermates, measured with CytotoxGlo assay. Increased cell death was observed in Tg2576 and arcAβ tg slices, although not significant in arcAβ tg slices, but not in E22ΔAβ tg slices. n = 9–16. B: Cytotoxicity in human tau expressing slices from wild-type mice treated with 1 μM recombinant Aβ. Treatment with wt Aβ42 and E22G Aβ42 but not E22Δ Aβ42, wt Aβ40, E22G Aβ40 or E22Δ Aβ40 increased cell death. n = 8–10 C: Cytotoxicity in slices from wild-type mice treated with 1 μM recombinant Aβ, in the absence of human tau expression. No toxicity was observed by wt Aβ42, E22G Aβ42 or E22Δ Aβ42 in the absence of human tau. n = 5. D: Representative western blot (left) of lysate of human tau expressing wild-type slices, treated with 1 μM recombinant Aβ, displaying total human tau, phospho-tau at the AT8 epitope and GAPDH. Quantification (right) of western blots showed increased tau phosphorylation after treatment with wt Aβ42 and E22G Aβ42 but not E22Δ Aβ42. n = 4. Data are means ± SD. Statistical significance was assessed by one-way ANOVA with Tukey's multiple comparison test (*p<0.05; **p<0.01, ***p<0.001).