Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson’s Disease Progression

Brit Mollenhauer*, Mohammed Dakna, Niels Kruse, Douglas Galasko, Tatiana Foroud, Henrik Zetterberg, Sebastian Schade, Roland G. Gera, Wenting Wang, Feng Gao, Mark Frasier, Lana M. Chahine, Christopher S. Coffey, Andrew B. Singleton, Tanya Simuni, Daniel Weintraub, John Seibyl, Arthur W. Toga, Caroline M. Tanner, Karl KieburtzKenneth Marek, Andrew Siderowf, Jesse M. Cedarbaum, Samantha J. Hutten, Claudia Trenkwalder, Danielle Graham

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The objective of this study was to assess neurofilament light chain as a Parkinson’s disease biomarker. Methods: We quantified neurofilament light chain in 2 independent cohorts: (1) longitudinal cerebrospinal fluid samples from the longitudinal de novo Parkinson’s disease cohort and (2) a large longitudinal cohort with serum samples from Parkinson’s disease, other cognate/neurodegenerative disorders, healthy controls, prodromal conditions, and mutation carriers. Results: In the Parkinson’s Progression Marker Initiative cohort, mean baseline serum neurofilament light chain was higher in Parkinson’s disease patients (13 ± 7.2 pg/mL) than in controls (12 ± 6.7 pg/mL), P = 0.0336. Serum neurofilament light chain increased longitudinally in Parkinson’s disease patients versus controls (P < 0.01). Motor scores were positively associated with neurofilament light chain, whereas some cognitive scores showed a negative association. Conclusions: Neurofilament light chain in serum samples is increased in Parkinson’s disease patients versus healthy controls, increases over time and with age, and correlates with clinical measures of Parkinson’s disease severity. Although the specificity of neurofilament light chain for Parkinson’s disease is low, it is the first blood-based biomarker candidate that could support disease stratification of Parkinson’s disease versus other cognate/neurodegenerative disorders, track clinical progression, and possibly assess responsiveness to neuroprotective treatments. However, use of neurofilament light chain as a biomarker of response to neuroprotective interventions remains to be assessed.

Original languageEnglish (US)
JournalMovement Disorders
DOIs
StateAccepted/In press - 2020

Keywords

  • Parkinson’s disease/parkinsonism
  • cohort studies
  • outcome research

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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