Fig. 1
From: Terminal complement pathway activation drives synaptic loss in Alzheimer’s disease models
Complement activation products in wildtype and AppNL−G−F mouse brain. a C1q levels in total brain homogenate (TBH) were significantly increased in AppNL−G−F at 3, 6, 9 and 12 months (m) compared to age-matched wildtype (WT) mice (n = 5–8). C1q levels in TBH remained stable with age in WT mice but increased with age in AppNL−G−F peaking at 9 months of age. One-way ANOVA with Tukey’s post-hoc test was used to test for differences between age groups of each genotype (dashed horizontal lines). Two-way ANOVA with Bonferroni post-hoc test was used to compare between genotypes at each age (solid horizontal lines). b Terminal complement complex (TCC) levels in TBH were significantly increased in AppNL−G−F mice at 3, 6, 9 and 12 months (m) compared to age-matched wildtype (WT) mice (n = 6–8). TCC levels in TBH showed a small but significant increase with age in WT mice, but were significantly and progressively increased at 6, 9 and 12 months in AppNL−G−F mice. One-way ANOVA with Tukey’s post-hoc test was used to test for differences between age groups of each genotype (dashed horizontal lines). Two-way ANOVA with Bonferroni post-hoc test was used to compare between genotypes at each age (solid horizontal lines). c C3 fragment levels in TBH at 6 months of age were significantly increased in AppNL−G−F compared to WT (n = 6). Unpaired two-tailed t-test. d C1q levels were highest in hippocampus (Hp), intermediate in cortex (Cx), and lowest in cerebellum (Cb) in WT and AppNL−G−F mice at 9 months. C1q levels were significantly increased in AppNL−G−F compared to age-matched WT in all regions (n = 6). Unpaired two-tailed t-test was used to compare between genotypes (solid horizontal lines) and between regions (dashed horizontal lines). e C3 fragments were highest in hippocampus, intermediate in cortex, and lowest in cerebellum in WT and AppNL−G−F mice at 9 months. C3 fragment levels were higher in AppNL−G−F mice compared to WT in all regions, significantly in cortex (n = 6). Mann–Whitney test was used to compare between genotypes (solid horizontal lines) and between regions (dashed horizontal lines). f TCC levels were highest in hippocampus, intermediate in cortex, and lowest in cerebellum in WT and AppNL−G−F mice at 9 months. TCC levels were significantly increased in AppNL−G−F compared to WT in all regions tested (n = 5–6). Unpaired two-tailed t-test was used to compare between genotypes (solid horizontal lines) and between regions (dashed horizontal lines). Error bars correspond to SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001