Neurofilament Light Chain in CSF and Plasma in Multiple System Atrophy – A Prospective, Longitudinal Biomarker Study
Wolfgang Singer1, Ann Schmeichel1, David Sletten1, Tonette Gehrking1, Jade Gehrking1, Jorge Trejo-Lopez1, Mariana Suarez1, Jennifer Anderson1, Pamela Bass1, Timothy Lesnick1, Phillip Low1
1Mayo Clinic
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.
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.
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.