Fig. 5
Increased aggregation, but reduced toxicity in a C. elegans model of AD. a–d Worms were treated at the L4 stage of development. a NIAD-4 staining of AD worms incubated in the absence (black) or presence of 10 µM (purple) and 20 µM (blue) doses of trodusquemine. Representative images at D6 are shown. **P < 0.01, ***P < 0.001 by Student’s t-test. Untreated control worms (grey) are shown for comparison. N = 20 per condition. b Motility, speed of swimming and the fraction of worms not paralyzed were monitored for AD worms incubated in the absence (N = 342) or presence of 10 µM (N = 352) and 20 µM (N = 309) doses of trodusquemine. These parameters were summed to generate fitness scores. **P < 0.01, ***P < 0.001 by Student’s t-test. Untreated control worms (N = 320) are shown for comparison. c Immunoblot measurements of the total Aβ levels in AD worms after treatment. Data shown are representative of duplicate blotting procedures. d Correlation between the concentration of trodusquemine administered and the increase in AD worm fitness (black, from b, *P < 0.05, ***P < 0.001 by one-way ANOVA), the relative quantity of aggregated Aβ42 (red, averages of D4 and D6 from a, *P < 0.05, ***P < 0.001 by one-way ANOVA) and the total levels of Aβ42 (blue, Supplementary Figure 13, NS: not significant by one-way ANOVA). All one-way ANOVA were followed by Bonferroni’s multiple comparison test relative to untreated AD worms. Panels b–d represent D5 of adulthood. e AD worms were also treated at D6 with (N = 88) and without 20 µM TRO (N = 105) and monitored at D7 for the conditions described in b. Fitness scores were calculated as above. ***P < 0.001 by Student’s t-test. Untreated (N = 434) and treated (N = 84) control worms (cyan) are shown for comparison. NS: not significant by Student’s t-test. All data represent mean ± s.e.m. (line thickness or error bar) with the N-values listed throughout. Aggregation and behavioural plots are representative of three biological replicates
