• Multiple sclerosis damages the lipid-rich myelin of nerve cells
• Lipid profile alterations are a hallmark of multiple sclerosis
• Lipidomics identified possible lipid biomarkers for diagnosis and treatment monitoring
IN multiple sclerosis (MS), a chronic inflammatory and neurodegenerative disease of the central nervous system, the body attacks the protective myelin sheath of neurons in the brain and the spinal cord. The damaged myelin causes communication problems between the central nervous system and the rest of the body. To this day, there is no cure for MS.
Neurobiological researchers believe that multiple sclerosis does not only cause the clinical symptoms we look for as of today but also alters a patient’s lipid metabolism. Detailed, molecular lipid analysis can discover specific biomarkers for MS to support fast and accurate diagnosis, better treatment, and monitoring.
Multiple sclerosis is the most common autoimmune disorder of the central nervous system. Globally, there are about 3 million people living with the disease, an estimated 300 people get diagnosed every day.
Lipid metabolism is critical to neural cell structure, function, and health. Thus, lipids are believed to play a critical role in multiple sclerosis and have direct or indirect effects on the progression of the neurodegenerative disease. First, myelin, the nerve’s protective sheath that is attacked in MS, consists mainly of lipids. Hence, a functioning lipid metabolism is critical for remyelination, the repair and reconstruction of myelin. But lipids are also critical for regulating inflammatory responses in neuroinflammation. Additionally, lipid metabolism is also important for general repair in the central nervous system.
MRI of a brain affected by multiple sclerosis: The brain MRI of a 30 year old man with relapsing remitting multiple sclerosis shows multiple lesions (white signals). S A Trip et al., Journal of Neurology, Neurosurgery & Psychiatry (2005), doi: 10.1136/jnnp.2005.073213
Similar to other neurodegenerative diseases such as Parkinson’s disease or Alzheimer’s disease, alterations in the lipid profile seem to be a hallmark of MS pathology. The dysregulation of lipid homeostasis and lipid metabolism in multiple sclerosis may affect the integrity of myelin and modulate neurodegeneration.
Individual diversity in symptoms and disease development make it hard to spot MS, especially early on. Patient’s must undergo various tests to get diagnosed, often leading to long suffering paths beforehand. Identifying specific blood biomarkers of multiple sclerosis might help improve patient life.
In order to discover such biomarkers researchers from the German Center for Neurodegenerative Diseases applied lipidomics analysis to blood plasma samples of 73 monozygotic twins in which only one of the twins was diagnosed with a form of MS – 243 distinct lipids were taken into account for further lipid data analysis.
Altered lipid classes and species in monozygotic twins discordant for multiple sclerosis:A On lipid class level, PC O- (***) and PE O- (**) are significantly decreased in MS-twins (dark blue = healthy twin, light blue = MS-twin). B Number of significantly altered lipid species (dark green) as parts of the whole corresponding lipid class. Horst Penkert et al., Annals of Clinical and Translational Neurology (2020), doi: 10.1002/acn3.51216
The results revealed no differences in total lipid content between the twin sibling with multiple sclerosis (MS-twins) and the healthy twin sibling. However, on the molecular level, ether phosphatidylcholine lipids (PC O-), and ether phosphatidylethanolamine lipids (PE O-) were reduced in MS-twins. In detail, 44% of PC O‐ and 47% of PE O‐ lipid species were altered. Surprisingly, the top hits for altered lipid species were dominated by PC O- lipids containing long polyunsaturated fatty acids (PUFAs).
PC O- and PE O- are both ether phospholipids, in which an ether bond attaches the fatty acid to the phospholipid instead of the more common ester bond. Ether phospholipids play an important role in inflammation and linked lipid signaling. They are rich in long PUFAs such as arachidonic acid. Eicosanoids, metabolic products of long PUFAs, are major signaling compounds in inflammation.
Phospholipids and ether-phospholipids: Phospholipids are lipids which contain a phosphate group, and two fatty acids. In ether phospholipids, one of the two fatty acids is not linked by an ester bond but by an ether bond. Shown are examples for phosphatidylcholine and ether-linked phosphatidylcholine.
Furthermore, ethers can bind to a transcription factor, that controls the readout of genes with metabolic and anti‐inflammatory functions. Thus, the reductions in ether lipids and PUFAs in MS-twins indicates altered lipid signaling in multiple sclerosis.
Among the 73 MS-twins, 20 twins did not receive a treatment for multiple sclerosis. Still, the altered lipid profile remained. This confirmed the change in PC O- and PE O- lipid levels was not linked to an MS treatment but to the disease itself.
Multiple sclerosis exhibits high interpersonal variance which limits our capability to predict individual disease courses. There is an unmet need for easily accessible biomarkers to help get a better understanding of the disease and support diagnosis and treatment.
Identifying lipids and specific lipid profiles as biomarkers for multiple sclerosis can open up various opportunities for scientific and medical treatment of the neuroinflammatory and neurodegenerative disease. Not only might it support a reliable diagnosis early on, but could also help in monitoring the disease development and the patient’s response to treatment.
The importance of lipids in relation to multiple sclerosis and other neuroinflammatory and neurodegenerative diseases is striking. Lipotype Lipidomics technology provides academic, industry and clinical researchers from neurobiology the means to find and identify specific lipid biomarkers in detailed lipidomics profiles.
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