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Lipid biomarkers for multiple sclerosis

Research Article

Diagnosing multiple sclerosis is difficult. Lipid markers can support diagnosis and treatment of the neuroinflammatory disease.

About the author


Olga (Olya) Vvedenskaya
Sci. Communications Officer

Dr. Dr. Olya Vvedenskaya studied medicine, and further obtained her PhD in the field of molecular oncology. She loves to deliver scientific messages in a clear and accessible manner.

Resources


Plasma lipidomics of monozygotic twins…

Penkert et al. | An Clin Trans Neurol (2020)


An automated shotgun lipidomics platform…

Surma et al. | EJLT (2015)


Systematic screening for novel lipids by…

Papan et al. | Anal. Chem. (2014)


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Summary

• 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 damage in the myelin sheath causes communication problems between the central nervous system and the rest of the body. To this day, there is no cure for MS, but there are medical options to ease the symptoms and number of relapses.

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.

Multiple sclerosis is the most common autoimmune disorder of the central nervous system. Globally, about 3 million people are living with the disease.

Symptoms of MS vary drastically within individuals, however, most patients report numbness and tingling feelings, fatigue, muscle spasms, stiffness and weakness, pain and mobility problems, and other symptoms. Such variability in symptoms and disease development makes it hard to spot MS, especially early on. Patients 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 terms of underlying pathological processes, researchers noticed changes in lipid metabolism in patients. 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 this neurodegenerative disease. Detailed, molecular lipid analysis can discover specific biomarkers for MS to support fast and accurate diagnosis, better treatment, and monitoring.

An infographic showing how neurons and their myelin sheaths are affected by multiple sclerosis, a chronic inflammatory and neurodegenerative disease of the central nervous system.

Myelin, the nerve’s protective sheath that is attacked in MS, consists mainly of lipids. Hence, functioning lipid metabolism is critical for remyelination, the repair and the 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.

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 development and manifestation. The dysregulation of lipid homeostasis and lipid metabolism in multiple sclerosis may affect the integrity of myelin and modulate neurodegeneration.

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 pointed out with arrows).

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 pointed out with arrows).
S A Trip et al., Journal of Neurology, Neurosurgery & Psychiatry (2005), doi: 10.1136/jnnp.2005.073213

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.

Graphs showing altered lipid classes and lipid species in blood plasma samples of patients with multiple sclerosis. Graph A highlights that the lipid class levels PC O- and PE O- are significantly decreased in multiple sclerosis. Graph B demonstrates that more than 40% of the lipid species belonging to the lipid classes PC O- and PE O- are significantly altered in multiple sclerosis.

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 twins with MS (dark blue = healthy twin, light blue = twin with MS). 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 and the healthy twin sibling. However, on the molecular level, ether phosphatidylcholine lipids (PC O-), and ether phosphatidylethanolamine were reduced in twins with MS. 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), that have the potential to be used as blood plasma multiple sclerosis biomarkers.

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.

A graphic comparison of 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.

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. The reductions in ether lipids and PUFAs in patients with MS indicate altered lipid signaling in multiple sclerosis. Among the 73 twins with MS, 20 patients did not receive 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 neuroinflammatory and neurodegenerative diseases. 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.

Lipotype Lipidomics technology provides academic, industry, and clinical researchers from neurobiology the means to find and identify specific lipid biomarkers in detailed lipidomics profiles of multiple sclerosis, Parkinson’s and Alzheimer’s diseases.

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DZNE


Logo of the DZNE, the German Center for Neurodegenerative Diseases.

The DZNE explores brain diseases. Their research is closely linked to clinical research, population studies, health care research and systems medicine, to identify new diagnostic markers and to enable rapid development of new therapies.


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