Neurofilament Light Chain to Predict Progression of Degenerative Brain Disorder
Assessing CSF and plasma NfL levels may help predict disease progression in PSP.
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VANCOUVER – Levels of neurofilament light chain (NfL) in cerebrospinal fluid (CSF) and plasma can help predict the rate of disease progression in patients with progressive supranuclear palsy (PSP).1
Results of the prospective study were presented at the 2017 International Congress of Parkinson's Disease and Movement Disorders.
Previous studies have demonstrated the utility of CSF NfL levels for the differentiation of atypical parkinsonian disorders from Parkinson's disease2; however there is limited evidence supporting the ability of serial measurements of CSF and plasma NfL to track and predict disease progression.3-5 With markers of clinical disease progression integral to the measurement of efficacy of disease-modifying therapies, a team of investigators led by Professor Huw Morris and Edwin Jabbari, MBBS, of University College London in the United Kingdom, sought to evaluate whether CSF and plasma NfL could predict the speed of PSP disease progression.
“The aim is to achieve a reliable plasma-based disease progression biomarker,” Dr Jabbari told Neurology Advisor. “This would be less invasive and preferable for patients compared with a CSF-based biomarker.”
A total of 115 patients and 30 healthy controls were recruited from 1 center from June 2011 to December 2013. Samples of CSF at baseline were collected from patients with PSP (n=33), corticobasal syndrome (CBS, n=11), multiple system atrophy (MSA, n=29), Parkinson's disease (PD, n=25), and Alzheimer's disease (AD, n=17) and controls. CSF NfL concentration was measured using enzyme-linked immunosorbent assay (ELISA) and plasma NfL concentration was measured with single molecule array (SIMOA). Baseline PSP rating scale (PSPRS) scores were obtained from patients with PSP and CBS on the same day as the CSF and plasma sample collections. Follow-up occurred longitudinally in order to assess total disease duration, which was defined as the number of days from motor onset to death or date of censoring (October 31, 2016).
Overall, the investigators found that CSF and plasma NfL levels were greater in patients with atypical parkinsonian syndromes (PSP, CBS, MSA; median CSF NfL: 2268.6 ng/mL; median plasma NfL: 42.4 pg/mL) compared with those with PD and AD and healthy controls (CSF NfL: 1116.0 ng/mL, 1273.1 ng/mL, and 630.6 ng/mL; plasma NfL: 21.8 pg/mL, 25.9 pg/mL, and 13.6 pg/mL, respectively). The investigators then divided the PSP patients into 3 groups (low, medium, high) based on CSF/plasma concentration tertiles:
|Baseline NfL levels||PSP CSF NfL (ng/mL)||PSP plasma NfL (pg/mL)|
After adjusting for sex, age at baseline, disease duration at baseline, and disease severity, the investigators found that compared with patients in the PSP-alone group in the lowest tertiles, the highest tertiles for CSF NfL and plasma NfL predicted an 11-fold (hazard ration [HR] 11.04; 95% CI, 1.96-62.02; P =.006) and 7-fold (HR 7.39; 95% CI, 1.05-52.18; P =.04) increase in risk of mortality. Further analysis also revealed a strong correlation between CSF and plasma NfL levels in the PSP-alone group (r=.83, P <.0001).
“These are promising data that show that baseline CSF and plasma NFL can predict the rate of disease progression in PSP,” Dr Jabbari told Neurology Advisor. “Further replication data are required, but the fact that levels of CSF and plasma NfL are so well correlated implies that plasma NfL may have a role in providing easily accessible early prognostic information for PSP patients.”
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- Jabbari E, Woodside J, Morris H. Can CSF and plasma neurofilament light chain predict disease progression in progressive supranuclear palsy? Presented at: 2017 International Congress of Parkinson's Disease and Movement Disorders. June 4-8, 2017; Vancouver, BC, Canada.
- Magdalinou N, Lees AJ, Zetterberg H. Cerebrospinal fluid biomarkers in parkinsonian conditions: an update and future directions. J Neurol Neurosurg Psychiatr. 2014;85(10):1065-1075.
- Boxer AL, Lang AE, Grossman M, et al. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 2014;13(7):676-685.
- Magdalinou NK, Paterson RW, Schott JM, et al. A panel of nine cerebrospinal fluid biomarkers may identify patients with atypical parkinsonian syndromes. J Neurol Neurosurg Psychiatr. 2015;86(11):1240-1247.
- Rojas JC, Karydas A, Bang J, et al. Plasma neurofilament light chain predicts progression in progressive supranuclear palsy. Ann Clin Transl Neurol. 2016;3(3):216-225.