The knowledge about the role of S1P-mediated signaling in AD is more recent, but indicates decreased levels of its endogenous ligand in cortical and subcortical areas in brain samples from AD patients [58] which, at least in the cortex, may be the consequence of aberrant functionality or altered expression of the S1P-synthesizing and/or degrading enzymes [59]. This evidence concerns the gene MBTPS1 and Alzheimer disease.