Abstract Details

Title Neurofilament Light Chain in CSF and Plasma in Multiple System Atrophy – A Prospective, Longitudinal Biomarker Study

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S9 - Autonomic Disorders (11:39 AM-11:51 AM)

Poster/Presentation
Number 003

Background Frequent misdiagnosis and challenges in quantifying disease progression underscore the critical need for reliable diagnostic biomarkers as well as surrogate markers of disease progression in MSA. NfL has been reported to potentially meet those needs.

Objective

To explore the value of neurofilament light chain (NfL) in plasma (NfL-p) in contrast to CSF (NfL-c) as diagnostic marker of multiple system atrophy (MSA), and to assess the value of NfL-p and NfL-c as marker of clinical disease progression.

Design/Methods Well-characterized patients with early MSA (n=32), Parkinson’s disease (PD, n=21), and matched controls (CON, n=15) were enrolled in a prospective, longitudinal study of synucleinopathies with serial annual evaluations. NfL was measured using a high sensitivity immunoassay, and findings were assessed by disease category and relationship with clinical measures of disease progression.

Results

Measurements of NfL-c were highly reproducible across immunoassay platforms (Pearson, r=0.99), while correlation between NfL-c and -p was only moderate (r=0.66). NfL was significantly higher in MSA compared to CON and PD; the separation was essentially perfect for NfL-c, but there was overlap, particularly with PD, for NfL-p. While clinical measures of disease severity progressively increased over time, NfL-c and -p remained at stable elevated levels within subjects across serial measurements. Neither change in NfL over time nor baseline NfL were significantly associated with changes in clinical markers of disease severity.

Conclusions These findings confirm NfL-c as faithful diagnostic marker of early MSA, while NfL-p showed less robust diagnostic value. The significant NfL elevation in MSA was found to be remarkably stable over time in both CSF and plasma and was not predictive of clinical disease progression, which has significant implications for the use of NfL in studies of disease modifying therapies in MSA, and argue against its use as a prognostic marker.

Authors/Disclosures
Wolfgang Singer, MD (Mayo Clinic) PRESENTER	Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UniQure. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Theravance. The institution of Dr. Singer has received research support from NIH. The institution of Dr. Singer has received research support from FDA. The institution of Dr. Singer has received research support from Michael J. Fox Foundation. Dr. Singer has received intellectual property interests from a discovery or technology relating to health care.
Ann M. Schmeichel	Ann M. Schmeichel has nothing to disclose.
David M. Sletten, MBA (Mayo Clinic)	Mr. Sletten has nothing to disclose.
Tonette Gehrking	Tonette Gehrking has nothing to disclose.
Jade Gehrking (Mayo Clinic, Neurology Dept)	Jade Gehrking has nothing to disclose.
Jorge Trejo-Lopez	No disclosure on file
Mariana Suarez	No disclosure on file
Jennifer Anderson	No disclosure on file
Pamela Bass	No disclosure on file
Timothy Lesnick	No disclosure on file
Phillip A. Low, MD, FAAN (Mayo Clinic)	Dr. Low has nothing to disclose.