Brain Tissue Lipidomics of Primary Progressive Multiple Sclerosis, Phenotypically Normal White Matter, and Controls

William Cheung, Yu-Shan Chen, Philip Day, Samrina Rehman

Research output: Contribution to conferenceAbstractpeer-review

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease characterised by immune-mediated demyelination and progressive loss of nerve fibres in the central nervous system (CNS). Lipids play a crucial role in MS pathogenesis as they are key components of myelin, the protective sheath surrounding nerve fibres. Dysfunction in lipid metabolism can hinder remyelination and contribute to neuroinflammation. Therefore, decoding the brain lipidome from myelin and identifying reliable biomarkers is essential to characterise and understand the underlying mechanisms of MS and predict its pathogenesis. Lipidomic analyses of affected brain regions could provide insights into metabolic alterations related to MS progression. A Thermo Vanquish UHPLC/IDX Tribrid high-resolution MS platform was employed for comprehensive lipidomics analysis. Post-mortem brain tissue samples from 7 primary progressive MS (PPMS) patients with active or chronic active lesions were compared to normal-appearing white matter (NAWM) samples from the same individuals (internal controls). Additionally, post-mortem brain tissue samples from 6 individuals without CNS diseases (non-CNS) served as external controls. Lipidomic components were extracted using a single-phase butanol/methanol method. Discovery lipidomic signatures were acquired, identifying 1251 lipids across 20 major lipid superclasses. All lipidated species were identified at both MS1 and MS2 levels using high-resolution mass spectrometry and validated against the in silico Lipidblast database, with a minimum MS/MS similarity of 70%. A total of 634 unique lipid species were retained for multivariate analysis. Extensive lipidomic alterations were detected in PPMS samples from the NAWM and controls. This indicates ongoing lipid metabolism dysregulation in areas appearing normal by imaging (macroscopically). The findings highlight the utility of lipidomics to uncover occult disease processes and provide insights into progressive MS pathology. This study demonstrates the value of lipidomic analysis of affected brain regions in elucidating lipid metabolic pathways involved in MS progression, beyond traditional large-scale profiling methods. The lipid changes are to be investigated for use as prognostic metabolic biomarkers.
Original languageEnglish
Publication statusPublished - 18 Oct 2023
EventELRIG DRUG DISCOVERY 2023: DIVERSE THINKING – NEW PERSPECTIVES - ACC, Liverpool, United Kingdom
Duration: 18 Oct 202219 Oct 2023
https://elrig.eventsair.com/dd23/posters

Conference

ConferenceELRIG DRUG DISCOVERY 2023: DIVERSE THINKING – NEW PERSPECTIVES
Country/TerritoryUnited Kingdom
CityLiverpool
Period18/10/2219/10/23
Internet address

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