We assessed the role of circulating cholesterol on the murine model of MS, the experimental autoimmune encephalomyelitis (EAE) disease using two different approaches: (1) the mouse model of familial hypercholesterolemia induced by low-density lipoprotein receptor (LDLr) deficiency, and (2) the use of the monoclonal anti-PCSK9 neutralizing antibody alirocumab, which reduces LDLr degradation and consequently lowers blood levels of cholesterol. This evidence concerns the gene LDLR and experimental autoimmune encephalomyelitis.