Fig. 5: CBA2 treatment reverses the effects of ApoE4 in a C. elegans model of AD and in targeted-replacement mice. | Communications Biology

Fig. 5: CBA2 treatment reverses the effects of ApoE4 in a C. elegans model of AD and in targeted-replacement mice.

From: Rescue of ApoE4-related lysosomal autophagic failure in Alzheimer’s disease by targeted small molecules

Fig. 5

a Images of transgenic C. elegans expressing Aβ42::mcherry in neurons. Red fluorescent aggregates are diminished after exposure to 10-µM CBA2 (lower panel). b Histogram of mean normalized Aβ42::mCherry intensities calculated from fluorescence images. Significance of inter-group differences was determined by 2-way ANOVA and Bonferroni post hoc; ****P < 0.0001 for N = 15–20 worms/group, represented as individual data points. c Chemotaxis index (CI) assessed on worms transduced with ApoE3 or ApoE4 protein, and treated with CBA2 for 5 days. CBA2 treatment improved chemotaxis in worms relative to either untreated worms or those receiving ApoE3 protein; *P < 0.02 by CHI.SQ test for N = 40–100 worms/group. Values are mean ± STDEV, (N = 2 repeats, represented as individual data points). Significance between CBA2-treated worms and control worms was determined by CHI.SQ test. d Western-blot analysis of key autophagy proteins in worms expressing ApoE4 ± CBA2. Protein bands shown in (d) were derived from the same blot that was stripped and re-probed with different antibodies. Histogram shows normalized band intensities calculated from western-blot images. Exposure to CBA2 significantly increased levels of SQST-1 and LAMP-2 in C.elegans. Significance of inter-group differences was determined by 2-way ANOVA and Bonferroni post hoc; *P < 0.02, ***P < 0.0003 versus control. e ApoE-TR3 (N = 3) and -TR4 mice (N = 8–9) were treated 12 h with CBA2 (47 μg/kg) or vehicle. RNA was prepared from liver, and mRNA levels of Sqstm1, Map1lc3a, Map1lc3b, and Lamp1 were assessed by qRT-PCR. *P = 0.0492; **P = 0.0066; main effect of CBA2 in ApoE-TR4 mice: P < 0.0001. Error bars indicate SEM. Three-way ANOVA was applied to test for potential main effects and interactions between the three variables in the overall experiment: genotype, treatment, and gene of interest. Differences within individual genes of interest were determined by 2-way ANOVA and Bonferroni post hoc.

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