Fig. 4

Terminal complement activation is ablated and hippocampal spine loss reduced in C6 deficient 3xTg-AD mice. a C3b/iC3b levels were significantly increased in TBH from 12–15 month 3xTg-AD mice compared with matched WT and reduced in 3xTg-AD C6^{−/ −}(n = 6; unpaired two-tailed t-test). b TCC levels were significantly increased in TBH from 3xTg-AD compared to WT; TCC levels were markedly reduced in 3xTg-AD C6^−/− mice (all 12–15 months; n = 6 per group; unpaired two-tailed t-test). c Representative confocal images of DiI labelled CA1 hippocampal dendritic segments from wild type (WT), 3xTg-AD and 3xTg-AD C6^−/−. Scale bar 5 µm. Spine densities were analysed from dendritic segments of at least 30 µm. DiI labelled dendritic spines were analysed from fresh hippocampal tissue slices and post-fixed following dye diffusion. d Spine density was significantly reduced in 3xTg-AD compared to WT; spine density in 3xTg-AD C6^−/− mice was significantly higher than in 3xTg-AD and not different from WT controls. WT, n = 4 mice, 3xTg-AD n = 7 mice and 3xTg-AD C6^−/− n 6 mice. One-way ANOVA with Tukey’s post-hoc test was used to test for differences between each genotype. e Sub-analysis of different spine types showed significant reduction in stubby and thin spines in 3xTg-AD mice compared to WT controls and 3xTg-AD-C6^−/−mice. One-way ANOVA with Tukey’s post-hoc test was used to test for differences between each genotype. f Representative images of Bassoon (green) and PSD95 (red) immunoreactive synaptic puncta in the stratum radium of 12-month-old WT, 3xTg-AD and 3xTg-AD C6^−/− mice. g Synaptic puncta, measured by staining with Bassoon or PSD95 and quantified (ROI; 20 µm × 20 µm, twelve per mouse) using Imaris Spot function were reduced in 3xTg-AD mice compared with either WT or 3xTg-AD C6^−/− mice (n = 4 per genotype), collated, and analysed. Unpaired two-tailed t-test was used to compare spine densities between genotypes. Scale bar 5 µm. Error bars correspond to SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001