Neurofilament Light Chain and Clinical Progression in Early...

Neurofilament Light Chain and Clinical Progression in Early Multiple System Atrophy

Daniel Claassen¹, Paula Trujillo Diaz¹, Amy Wynn¹, Bailu Yan², Hakmook Kang¹, Margaret Bradbury³, Cynthia Wong³, David Stamler^3
1Vanderbilt University Medical Center, ²Vanderbilt University, ³Alterity Therapeutics

Objective:

To assess one-year progression of biomarkers and clinical symptoms in Multiple System Atrophy (MSA)

Background:

Fluid biomarkers potentially quantify disease severity, monitor disease progression, and predict clinical symptoms in MSA. We assessed changes in clinical severity and neurofilament light chain (NfL) over a 12-month period.

Design/Methods:

We enrolled 15 participants who met criteria for clinically possible or probable MSA. Neurologic examination and clinical assessments included the Unified Multiple System Atrophy Rating Scale (UMSARS part 1 and 2) and the Natural History and Neuroprotection in Parkinson Plus Syndromes (PPS) rating scale (assessing motor severity). Plasma neurofilament light chain (NfL) was obtained every 3 months, and cerebral spinal fluid (CSF) every 6 months. Longitudinal changes were assessed using a random effects model with random intercept. Clinical associations were assessed using a linear regression model.

Results:

Across all participants, plasma NfL increased at an average rate of 0.56 pg/mL/month (p<0.001). The rate of CSF NfL increase over time was not statistically significant. There was a significant correlation between plasma and CSF NfL levels (r= 0.63, p=0.04), and over time one standard deviation increase in CSF NfL correlated with a 0.7304 standard deviation increase in plasma NfL (r= 0.7304 p<0.001). To evaluate the associations between baseline NfL and clinical symptoms over time, we applied a simple linear regression, using baseline plasma or CSF NfL as a predictor of clinical change at 6 and 12 months. Baseline plasma and CSF NfL were independently associated with 6 and 12-month change in total PPS and UMSARS part 2 (p<0.05). Plasma NfL was additionally associated with 6 and 12-month progression of UMSARS part 1 (p<0.05).

Conclusions:

Plasma and CSF NfL are associated with clinical worsening in MSA. Plasma NfL significantly increased over 12 months. These data suggest that NfL may be a marker of disease modification in studies of MSA.