Lipid Biomarkers in Multiple Sclerosis Pathogenesis
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The purpose of the work presented in this dissertation was to investigate the role of cholesterol metabolism in the pathogenesis of multiple sclerosis (MS). Serum lipid profile measures have previously been shown to be associated with disability and lesion formation in MS patients. While the central nervous system (CNS) requires cholesterol for many functions, it is unable to cross the blood brain barrier (BBB), and therefore the brain relies on de novo synthesis of cholesterol. The interactions between peripheral and CNS cholesterol networks are not well understood. A portion of this research focuses on the associations between serum lipid profile measures and various clinical outcome measures, biological measures and immunological markers. Oxysterols are cholesterol metabolites that are able to cross the BBB and mediate interactions between the periphery and the CNS. In order to further understand the role of cholesterol in MS, this dissertation also assessed how oxysterol levels differ between MS patients and healthy controls at baseline and over 5 years, and how these oxysterol levels are associated with serum lipid profile measures. The final part of this dissertation investigates the changes in cholesterol measures in response to both interferon-b1a treatment and after following a multimodal dietary intervention. The main findings from this research are that i.) baseline high density lipoprotein cholesterol (HDL-C) is protective against BBB breakdown, ii.) changes in lipid profile measures are associated with MS clinical outcome measures, iii.) cholesterol may be interacting with specific immune cells in multiple sclerosis patients on interferon-b1a, and iv.) oxysterol levels differ in MS patients compared to healthy controls.