Fig. 2

Brain ceramides are robustly elevated in PS19 mice and are normalized with PDDC treatment. a Plasma and brain levels of PDDC measured over 24 h following 4 weeks of dosing. N = 3/group at each time point. Points represent mean ± SEM. b Dosing schematic. c Percent change of body weight at the time of sacrifice from the maximum body weight over a 5-month dosing period in the WT + Vehicle, PS19 + Vehicle, and PS19 + PDDC groups. N = 16–20. d Quantification of hippocampal nSMase2 activity in the WT + Vehicle, PS19 + Vehicle, and PS19 + PDDC mice. N = 8–10/group. e Heatmap showing the ceramide species significantly reduced in PDDC-treated PS19 mice compared to vehicle-treated PS19 mice (P < 0.05). Colors represent relative abundance of each ceramide. f–p Cortical ceramide levels in WT and PS19 mice chronically treated with vehicle or PDDC. N = 6–11/group. Bars represent mean ± SEM. *P < 0.05. **P < 0.01. ***P < 0.001. One-way ANOVA with Tukey’s multiple comparison