APP and Alzheimer disease: To this end, we assessed brain and plasma ceramide and S1P profiles in APOE4 and APOE3 transgenic mice with or without five familial AD mutations (E4FAD or E3FAD; K670N/M671L, I716V, and V717I in the APP gene and M146L and L286V in the PS1 gene) (Tai et al., 2011; Youmans et al., 2012a,b).