The Role of Lipid Alteration in Multiple Sclerosis

Multiple sclerosis (MS) is traditionally recognized as a chronic immune-mediated disorder of the central nervous system (CNS), but increasing evidence suggests that systemic metabolic alterations may also contribute to its pathophysiology. Lipid abnormalities in MS have recently attracted renewed research interest, with studies focusing both on dysregulation of lipid signaling pathways and on alterations in standard lipid profile components, including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), and non-HDL cholesterol. Although disturbances in serum lipid profiles are consistently reported in patients with MS, their origin remains unresolved. Emerging data indicate that dyslipidemia may stem from aberrant cholesterol metabolism within the CNS, secondary to demyelination and myelin sheath destruction, leading to the release of lipid-rich debris and subsequent systemic metabolic imbalance. These lipid changes appear to correlate with blood-brain barrier (BBB) dysfunction, suggesting a link between peripheral lipid metabolism and CNS inflammation. This review summarizes current knowledge on the mechanisms underlying dyslipidemia in MS, its potential impact on disease progression, and its relevance as a possible therapeutic or biomarker target in future translational studies.