Lipid Profiles and Neurological Outcomes in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic disorder characterised by inflammatory demyelination and neurodegeneration within the central nervous system (CNS). Lipid metabolism influences both structural integrity of myelin sheaths and immune cell function. Alterations in serum lipoprotein levels—including low-density lipoprotein (LDL), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL) and triglycerides—have been associated with disease activity, disability progression and blood–brain barrier (BBB) permeability. Dyslipidaemia may exacerbate endothelial dysfunction, promote monocyte infiltration and modulate cytokine profiles. Conversely, specific lipid fractions and apolipoproteins display neuroprotective or anti-inflammatory properties that may preserve myelin and reduce lesion formation. Strategies targeting lipid homeostasis—such as statin therapy, dietary modification and pharmacological elevation of HDL—offer promising adjuncts to current immunomodulatory treatments. Understanding the complex interplay between systemic lipid profiles and neurological outcomes is crucial for biomarker development and personalised therapeutic approaches in MS.

Research from Nature Portfolio

Analysis of relapsing–remitting MS (RRMS) patients using nuclear magnetic resonance spectroscopy has revealed a distinct lipoprotein signature characterised by smaller LDL particles, increased small HDL (sHDL) in low body mass index cohorts and enlarged triglyceride-rich VLDL. These changes coincide with impaired cholesterol efflux capacity, altered apolipoprotein A-I composition and reduced ability of HDL subfractions to suppress monocyte inflammatory activity. A separate study has quantified lipids within specific VLDL and HDL subclasses, reporting that free cholesterol carried by the VLDL-2 subfraction correlates strongly with Expanded Disability Status Scale scores and with pro-inflammatory cytokines. Together, these findings implicate subfraction-specific lipoprotein alterations in MS pathophysiology and suggest potential targets for modulating systemic inflammation and neurodegeneration.

Lipid Profiles and Neurological Outcomes in Multiple Sclerosis publication trend

The graph below shows the total number of articles in lipid profiles and neurological outcomes in multiple sclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

High-density lipoprotein (HDL): Serum particles that transport cholesterol from peripheral tissues to the liver for excretion and exhibit anti-inflammatory functions.

Low-density lipoprotein (LDL): Lipoprotein particles that deliver cholesterol to tissues and may promote endothelial dysfunction when elevated.

Very low-density lipoprotein (VLDL): Triglyceride-rich lipoprotein secreted by the liver that delivers lipids to peripheral tissues.

Apolipoprotein A-I: The main protein component of HDL, critical for cholesterol efflux and anti-inflammatory properties.

Blood–brain barrier (BBB): A selective vascular interface that regulates passage of cells and molecules into the CNS.

Cholesterol efflux: The process by which cells remove excess cholesterol, often mediated by HDL and its transporters.

Mendelian randomisation: A genetic epidemiology method that uses inherited variants as proxies to infer causal relationships between risk factors and disease.

References

1. Increased cholesterol synthesis drives neurotoxicity in patient stem cell-derived model of multiple sclerosis. Cell Stem Cell (2024).
2. Protective Role of High-Density Lipoprotein in Multiple Sclerosis. Antioxidants (2024).
3. Exploring the Role of Plasma Lipids and Statin Interventions on Multiple Sclerosis Risk and Severity. Neurology (2023).
4. Relapsing-remitting multiple sclerosis patients display an altered lipoprotein profile with dysfunctional HDL. Scientific Reports (2017).
5. Lipoprotein markers associated with disability from multiple sclerosis. Scientific Reports (2018).