Abstract Details

Title Oxysterols and Apolipoproteins in Multiple Sclerosis: A 5-year Follow-up Study

Topic Multiple Sclerosis

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-073

Objective To investigate whether changes in oxysterol and apolipoprotein levels over 5 years are associated with disease course and disability progression in multiple sclerosis (MS).

Background

Cholesterol is required for myelin structure and proper functioning of neuronal cells in the CNS. Cholesterol and lipoproteins do not cross the BBB, so the brain is dependent on de novo cholesterol synthesis.

Oxysterols are oxygenated cholesterol metabolites that traverse the BBB and act as signaling mediators between the periphery and the CNS to enable the maintenance of brain cholesterol homeostasis. We investigated 3 side chain oxysterols: 24-hydroxycholesterol (24HC), 25-hydroxycholesterol (25HC) and 27-hydroxycholesterol (27HC), and two B-ring oxysterols: 7-hydroxycholesterol (7αHC) and 7-ketocholesterol (7KC). 24HC is produced exclusively in the brain, and is the primary regulator of cholesterol synthesis and the principal mechanism for cholesterol elimination in the brain

Design/Methods This study included 139 subjects (39 healthy controls, (HC), 61 relapsing-remitting MS (RR-MS), 39 progressive MS (P-MS)). 24HC, 25HC, 27HC, 7aHC and 7KC were measured at baseline and 5-years using a novel mass spectrometric method, and apolipoproteins (Apo) were measured using immunoturbidometric diagnostic kits.

Results

Levels of 24HC (p = 0.004), 25HC (p = 0.029) and 27HC (p = 0.026) increased in P-MS patients. 7KC (p = 0.047) and 7aHC (p = 0.001) levels decreased in RR-MS patients; there were no changes in any oxysterols in HC.

In MS patients, ApoCII (all p ≤ 0.01) and ApoE (all p ≤ 0.01) changes were positively associated with all oxysterol levels.

Increases in 24HC (p = 0.038) and ApoB (p = 0.038) and decreases in 7KC (p = 0.020) were observed in RR-MS patients who converted to SP-MS at follow-up and in SP-MS patients compared to RR-MS patients.

Conclusions Oxysterols and their associations with apolipoproteins differed between MS and HC over 5-years. Oxysterol and apolipoprotein changes were associated with conversion to SP-MS.

Authors/Disclosures
Murali Ramanathan, PhD (University At Buffalo) PRESENTER	The institution of Dr. Ramanathan has received research support from DoD. Dr. Ramanathan has received publishing royalties from a publication relating to health care.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Dejan Jakimovski, MD, PhD (Buffalo Neuroimaging Analysis Center, University at Buffalo)	Dr. Jakimovski has nothing to disclose.
Jesper Hagemeier	No disclosure on file
	No disclosure on file
Bianca Weinstock-Guttman, MD (Department of Neurology, University At Buffalo)	Dr. Weinstock-Guttman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme &Sanofi. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving as a Reviewer with NIH.
Robert Zivadinov, MD, PhD, FAAN (Buffalo Neuroimaging Analysis Center)	The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Omnicuris. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Myrobalan. Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen.

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