Abstract Details

Title Metabolomic Profiling of Multiple Sclerosis Lesions and Periplaque White Matter Demonstrates Extensive Changes in Lipid Metabolism

Topic Multiple Sclerosis

Presentation(s) P2 - Poster Session 2 (11:45 AM-12:45 PM)

Poster/Presentation
Number 3-010

Objective

To identify whether there are differences between the brain tissue metabolome in people with multiple sclerosis (PwMS) compared to controls and between the different type of MS lesions

Background

MS is characterized by immune-mediated white matter (WM) demyelination and consecutive axonal loss. Whether this process alters the metabolome in the affected brain areas is not clear.

Design/Methods Brain tissues, obtained from 5 PwMS and 12 controls, were sent for metabolomic analysis. In PwMS, tissues were extracted from the edge and core of demyelinated WM chronic active and inactive lesions, and periplaque WM, while in controls they were dissected from normal WM. Weighted gene correlation network analysis (WGCNA) were utilized to cluster highly correlated metabolites together into modules. We then applied generalized estimating equations models to compare WGCNA-module scores between different tissues, accounting for multiple metabolomic profiles contributed by some subjects.

Results

MS lesions were found to have decreased concentrations of hexosylceramides (p = 0.019), glycero-phospholipids (p = 3.6E−7), nucleotide metabolites (p = 5.0E−4), and long-chain fatty acids (p = 1.6E−6) and increased concentrations of dipeptides/sugars (p = 0.0063), sphingosines (p = 0.0026), phospholipids (p = 0.0019), sphingomyelines and ceramides (p = 4.4E−10) compared to control WM. In MS periplaques there were decreased levels of glycerol-phospholipids (p = 0.017) and long-chain fatty acids (p = 0.014) and increased levels of sphingomyelines and ceramides (p = 0.0026) compared to control WM.

Conclusions

Myelin lipids were significantly altered in MS with more prominent differences in lesions, and these could potentially act as biomarkers of inflammation and neurodegeneration in PwMS.

Authors/Disclosures
Dimitrios C. Ladakis, MD (Johns Hopkins University, School of Medicine) PRESENTER	Dr. Ladakis has nothing to disclose.
Martina Absinta, MD	Dr. Absinta has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Absinta has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abata Therapeutics. The institution of Dr. Absinta has received research support from International MS Alliance. The institution of Dr. Absinta has received research support from FRRB Early Career Award. The institution of Dr. Absinta has received research support from Cariplo Foundation.
Maria I. Reyes-Mantilla, MD (Johns Hopkins University, Neurology)	Dr. Reyes-Mantilla has nothing to disclose.
Carlos A. Pardo-Villamizar, MD (Johns Hopkins U, Med Dept of Neurology)	The institution of Dr. Pardo-Villamizar has received research support from National Institutes of Health. The institution of Dr. Pardo-Villamizar has received research support from Bart McLean Fund for Neuroimmunology Research .
Pavan Bhargava, MD, FAAN (Johns Hopkins University)	The institution of Dr. Bhargava has received research support from EMD Serono. The institution of Dr. Bhargava has received research support from Amylyx pharmaceuticals. The institution of Dr. Bhargava has received research support from Genentech. The institution of Dr. Bhargava has received research support from GSK.

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