Moreover, primary bone marrow-derived MC (BMMC) activated in vitro by exogenous S1P, which we established as a key in vivo MC stimulus in pre-symptomatic AD [15], exhibited elevation of Cer C16 and C24 species with corresponding increased gene expression of CerS 4, 5 and 6 and Asah1. We propose that the MC/Cer axis is an essential pathogenic enabler of pre-lesional AD. This evidence concerns the gene CBLN1 and Alzheimer disease.