Fig. 1

Treatment with sAPPα but not sAPPβ reduces Aβ-induced tau phosphorylation and dendritic spine loss. a Oligomeric Aβ preparations were characterized by SDS-PAGE followed by silver staining (left panel) or western blot using 6E10 antibody (right panel). Besides monomers, trimers and tetramers were the main Aβ species obtained by the used oligomerization protocol. b Primary neuronal cultures overexpressing human 441 tau were treated with 500 nM oligomeric Aβ or scrambled control and 400 ng/ml sAPPα or sAPPβ. AT8 and AT180 phosphorylation was detected in cell lysates. c Quantification of western blots. Aβ oligomers increased AT8 and AT180 phosphorylation of tau which was prevented by 400 ng/ml sAPPα but not sAPPβ. Statistical comparison between multiple groups was performed using one-way ANOVA with Tukey’s test for multiple comparisons n = 5 (*, p < 0,05; **, p > 0,01; ***, p < 0.001;). For important non-significant results, the exact p-values are displayed. d Representative images of CA1 apical dendritic segments of organotypic hippocampal slice cultures expressing eGFP. Slices were treated with 500 nM oligomeric Aβ or scrambled control and 400 ng/ml sAPPα or sAPPβ. scale bar = 5 μm e Analysis of dendritic spine density displayed as spine counts per μm dendrite. Spine density was strongly reduced by Aβ treatment. sAPPα but not sAPPβ diminished dendritic spine loss caused by Aβ. Statistical comparison between multiple groups was performed using one-way ANOVA with Tukey’s test for multiple comparisons n = 7–11, Hippocampal slices were prepared from at least 3 different mice per condition. (**, p > 0,01; ***, p < 0.001;). For important non-significant results, the exact p-values are displayed. Scr. Aβ: scrambled Aβ; AβO: oligomeric Aβ