Â鶹´«Ã½Ó³»­

Â鶹´«Ã½Ó³»­

Explore the latest content from across our publications
Join The Â鶹´«Ã½Ó³»­

Log In

Forgot Password?
Create New Account

Loading... please wait

Abstract Details

Acute and Chronic Demyelination Independent of Inflammation Promotes Tissue- and Blood-markers of Neuroaxonal Pathology
Multiple Sclerosis
S17 - Multiple Sclerosis: Immunology/Basic Sciences (2:48 PM-3:00 PM)
010
To determine whether standalone oligodendrocyte and myelin damage do not only increase neuronal vulnerability but are sufficient to cause neuroaxonal injury.
Neuroaxonal injury is a significant driver of permanent disability in various neurological conditions, despite heterogeneous underlying pathophysiologies. Accurate understanding of common drivers of neuroaxonal loss is critical for developing broadly effective neuroprotective strategies.
Neurofilament-light chain (NfL)-based tissue and blood markers reflected the magnitude of neuroaxonal pathology in both immune-mediated demyelination (experimental autoimmune encephalomyelitis [EAE]) and non-immune-mediated demyelination models (conditional knockout of Myrf transcription-factor in oligodendrocyte [MyrfΔiPLP]). To confirm the findings in a human demyelinating condition, multiple sclerosis, novel blood markers of myelin injury (MOG), and oligodendrocyte injury (OMgp), we evaluated samples from people with MS (pwMS).
In EAE, serum NfL was significantly elevated at day 21 post-immunization (mean 5007 pg/ml) compared to age-matched sham mice (229.6, p=0.004). EAE-derived spinal cord lesions showed higher number NfL DegenoTag-positive axons at EAE peak, which colocalized with inflammatory cell infiltration and myelin loss. In MyrfΔiPLP mice, NfL levels were substantially elevated at the peak of demyelination at week 10 post tamoxifen relative to wild-type controls (303.8 vs. 46.6 pg/ml, p<0.001) and were substantially reduced during remyelination (134.6, p= 0.001). Moreover, blood NfL levels matched DegenoTag staining in spinal cord white matter. In stable non-active pwMS, serum MOG and OMgp levels were associated with higher NfL (Estimate 0.62 [95%CI 0.36 – 0.89] and 0.19 [0.08 – 0.30], p≤0.001 for both). In addition, delayed VEP latency correlated with NfL levels (0.02 [0.01 – 0.03], p=0.003).
Our study provides a translational framework for understanding neuroaxonal injury in demyelinating conditions. Tissue and blood NfL-based markers of neuroaxonal injury increased following demyelination and exhibited a dose-dependent effect. Remyelination was associated with reduction of NfL-based evidence of neuroaxonal pathology. Myelin integrity appears to be crucial for maintaining axonal health. 
Authors/Disclosures
Ahmed Abdelhak, MD (UCSF Weill Institute of Neuroscience)
PRESENTER 		The institution of Dr. Abdelhak has received research support from German Multiple Sclerosis Society.
Christian Cordano, MD, PhD (UCSF) Dr. Cordano has nothing to disclose.
Katie Emberley (Oregon Health & Science University) No disclosure on file
Greg Duncan (OHSU) No disclosure on file
Sonia Nocera (UCSF) No disclosure on file
Kirtana Ananth An immediate family member of Kirtana Ananth has received personal compensation in the range of $10,000-$49,999 for serving as a Whole Time Member with Securities and Exchange Board of India (SEBI).
Nora Jabassini No disclosure on file
Kiarra Ning No disclosure on file
Henriette Reinsberg No disclosure on file
Frederike Cosima Oertel, MD (University of California, San Francisco) The institution of Dr. Oertel has received research support from Â鶹´«Ã½Ó³»­. The institution of Dr. Oertel has received research support from Hertie Foundation. Dr. Oertel has received personal compensation in the range of $500-$4,999 for serving as a Recipient (Travel Grant) with ECTRIMS. Dr. Oertel has received personal compensation in the range of $500-$4,999 for serving as a Recipient (Travel Grant) with NMSS. Dr. Oertel has received personal compensation in the range of $500-$4,999 for serving as a Recipient (Travel Grant) with ACTRIMS.
Alexandra Beaudry-richard (UCSF) Alexandra Beaudry-richard has received research support from the Multiple Sclerosis Society of Canada. Alexandra Beaudry-richard has received research support from the Canadian Institutes of Health Research .
Jens Kuhle, MD Dr. Kuhle has nothing to disclose.
Trent Watkins (University of California at San Francisco) No disclosure on file
Jonah Chan, PhD (UCSF) Jonah Chan, PhD has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Contineum Therapeutics. Jonah Chan, PhD has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for SFN. Jonah Chan, PhD has stock in Contineum Therapeutics. The institution of Jonah Chan, PhD has received research support from Mead Johnson. Jonah Chan, PhD has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with NIH/NINDS.
Ben Emery (Oregon Health & Science University) No disclosure on file
Ari Green, MD (UCSF) Dr. Green has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. The institution of Dr. Green has received research support from Department of Defense. The institution of Dr. Green has received research support from Department of Defense. The institution of Dr. Green has received research support from NIH. The institution of Dr. Green has received research support from NIH / NINDS. The institution of Dr. Green has received research support from NIH / NINDS. Dr. Green has received intellectual property interests from a discovery or technology relating to health care.