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Abstract Details

Evaluating the Correlation Between Spinal Fluid and Blood Levels of Neurofilament Light, GFAP, Tau, and UCHL1: Do We Need a Correction Factor in Evaluating Blood Levels?
Multiple Sclerosis
S49 - Multiple Sclerosis: Basic Science (2:36 PM-2:48 PM)
009

To evaluate factors contributing to blood and cerebrospinal fluid(CSF) discordance and determine if a correction of blood levels can better estimate what is happening in the CSF compartment.

Plasma neurofilament light(pNFL) levels account for 30-60% of the variance in CSF neurofilament light(cNFL) levels depending on the study. Age, disability, relapses, and the presence of contrast enhancing MRI lesions can increase both pNFL and cNFL. Additional nervous system biomarkers can now be studied in plasma. Understanding the factors that increase their variability in blood may be helpful in normalizing levels to better understand what levels are concerning for ongoing disease activity.

Matched plasma and CSF samples were identified in the Rocky Mountain Multiple Sclerosis Center Biorepository at the University of Colorado. Neurofilament Light(NFL), Glial Fibrillary Acidic Protein(GFAP), tau, and Ubiquitin carboxy-terminal hydrolase L1(UCHL1) levels were assessed using Single Molecule Array(SIMOA) in a Quanterix SR-X machine. Analyses were done on log transformed NFL concentrations.

Fifty-seven patients had matched plasma and cerebrospinal fluid samples evaluated for neurofilament light which included 24 patients with multiple sclerosis(MS), 7 with neuromyelitis optica spectrum disorder(NMOSD), and 18 patients with headache whose opening pressures were <20cmH2O. These patients had a mean age of 46.5(+/-11.2) years, 75% female, mean albumin index of 6.3(+/-5.5), and BMI of 27.4(+/-5.8).  The CSF and plasma concentrations in pg/ml were for NFL 1059.3(+/-3052.4) and 12.2(+/-32.4), GFAP 7621.5(+/-9713.4) and 52.9(+/-39.7), tau 41.5(+/-41.3) and 1.3(+/-0.8), UCHL1 1356.0(+/-1677.1) and 23.6(+/-32.8). Respectively the CSF vs plasma Spearman correlations (95% confidence intervals, p values) were: 0.79(0.67-0.87,<0.0001), 0.67(0.50-0.79,<0.0001), 0.75(0.61-0.85,<0.0001), and 0.70(0.54-0.81,<0.0001). Adjusting individually for age, BMI, or albumin index did not affect the correlation for NFL.

Blood and CSF levels of NFL, GFAP, tau, and UCHL1 correlated well. Models will be created that explore the relationship between Blood and CSF levels of these biomarkers.
Authors/Disclosures
Enrique Alvarez, MD, PhD (University of Colorado)
PRESENTER 		Dr. Alvarez has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Alvarez has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Alvarez has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Alvarez has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Alvarez has received personal compensation in the range of $50,000-$99,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Alvarez has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene/BMS. The institution of an immediate family member of Dr. Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Alvarez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon.
No disclosure on file
Kavita Nair, PhD, FAAN (University of Colorado) Dr. Nair has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Meyers Squibb. Dr. Nair has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Nair has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for PhRMA Foundation. Dr. Nair has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Nair has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Nair has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MJH Lifesciences. Dr. Nair has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Nair has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Nair has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Nair has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Anylam . Dr. Nair has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Applied Patient Experience. Dr. Nair has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Esai. Dr. Nair has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for MHJ Life Sciences. Dr. Nair has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi-Genzyme. Dr. Nair has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen. Dr. Nair has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for ICER. The institution of Dr. Nair has received research support from Genentech. The institution of Dr. Nair has received research support from Novartis. The institution of Dr. Nair has received research support from Genentech. The institution of Dr. Nair has received research support from Phrma Foundation. The institution of Dr. Nair has received research support from Bristol Meyers Squibb. The institution of Dr. Nair has received research support from Novartis. The institution of Dr. Nair has received research support from NINDS. The institution of Dr. Nair has received research support from Sanofi Genzyme. The institution of Dr. Nair has received research support from Kyverna Therapeutcis. Dr. Nair has a non-compensated relationship as a Board Member with Center for Improving Value in Healthcare that is relevant to AAN interests or activities.
Robert H. Gross, MD, FAAN (University of Colorado) Dr. Gross has nothing to disclose.
Amanda L. Piquet, MD, FAAN (University of Colorado) The institution of Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech/Roche. The institution of Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Kyverna . The institution of Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech/Roche. The institution of Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kyverna. The institution of Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Sands Anderson PC. Dr. Piquet has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Joe Jones Law Firm. The institution of Dr. Piquet has received research support from Rocky Mountain MS Center. The institution of Dr. Piquet has received research support from Novartis. The institution of Dr. Piquet has received research support from Abbvie. The institution of Dr. Piquet has received research support from Roche/Genentech. The institution of Dr. Piquet has received research support from NYU. The institution of Dr. Piquet has received research support from Anokion. The institution of Dr. Piquet has received research support from UCB . The institution of Dr. Piquet has received research support from Foundation for Sarcoidosis. The institution of Dr. Piquet has received research support from Kyverna . Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received publishing royalties from a publication relating to health care. Dr. Piquet has received personal compensation in the range of $10,000-$49,999 for serving as a Litigative Consultant with US-Dept HHS/DICP. Dr. Piquet has a non-compensated relationship as a Medical Advisory Board Member with Autoimmune Encephalitis Alliance (AEA) that is relevant to AAN interests or activities. Dr. Piquet has a non-compensated relationship as a Medical Advisory Board Member with Stiff Person Syndrome Research Foundation (SPSRF) that is relevant to AAN interests or activities.
Courtney Knapp No disclosure on file
Sean Selva Sean Selva has nothing to disclose.
Stefan Sillau Stefan Sillau has nothing to disclose.
Jeffrey L. Bennett, MD, PhD, FAAN (University of Colorado School of Medicine) Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Amgen. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Tanabe. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immpact Bio. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Chugai. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Beigene. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Imcyse. Dr. Bennett has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MIAC. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CorEvitas. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Vindico. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Touch IME. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Efficient LLC. Dr. Bennett has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Pavich. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Marie Bush. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Marks Gray. Dr. Bennett has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Knight, Nicastro, MacKay. The institution of Dr. Bennett has received research support from Alexion. Dr. Bennett has received intellectual property interests from a discovery or technology relating to health care. Dr. Bennett has received publishing royalties from a publication relating to health care.
Gregory Owens, PhD Dr. Owens has received intellectual property interests from a discovery or technology relating to health care.
Timothy L. Vollmer, MD, FAAN The institution of Dr. Vollmer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen IDEC. The institution of Dr. Vollmer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech/Roche. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Siranax. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Meyers Squib. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bios. The institution of Dr. Vollmer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. The institution of Dr. Vollmer has received research support from Rocky Mountain MS Center. The institution of Dr. Vollmer has received research support from Biogen. The institution of Dr. Vollmer has received research support from Actelion. The institution of Dr. Vollmer has received research support from Genentech/Roche. The institution of Dr. Vollmer has received research support from Anokion. The institution of Dr. Vollmer has received research support from TG Therapeutics.