Figure 6.

Predictions of Alzheimer disease (AD)‐relevant modulations for sphingosine‐1‐phosphate 5 receptor S1 (PR5) agonist A‐971432 using the quantitative systems pharmacology (QSP) model, and in modulation observed in vivo in an aged mouse model. (a) Predicted modulation of sphingosine‐1‐phosphate (S1P), ceramide (Cer), soluble and insoluble amyloid beta (Aβ)1‐42 in the brain, as well as soluble Aβ1‐42 in cerebrospinal fluid (CSF), after once daily dosing for 10 weeks (Color code: black: healthy BL, red: AD baseline, blue: 0.03 mg/kg, green: 1 mg/kg, magenta: 3 mg/kg). Note that for S1P all simulation curves for AD lie on top of each other. (b) Results for S1P, Cer, and soluble Aβ1‐42 (RAB fraction) in the brains of young and aged SAMP8 mice treated with vehicle or different oral doses of A‐971432 once daily for 10 weeks. Bars represent means and error bars indicate the standard errors of mean. Significant differences are indicated: ^{^} P < 0.05 in comparison with young vehicle treated animals; * P < 0.05, ** P < 0.01, in comparison with aged vehicle treated animals.