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 Kieburtz; Kenneth Marek; Andrew Siderowf; Jesse M Cedarbaum; Samantha J Hutten; Claudia Trenkwalder; Danielle Graham

doi:10.1002/mds.28206

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

Mov Disord. 2020 Nov;35(11):1999-2008. doi: 10.1002/mds.28206. Epub 2020 Aug 15.

Authors

Brit Mollenhauer^{1

2}, Mohammed Dakna¹, Niels Kruse³, Douglas Galasko⁴, Tatiana Foroud⁵, Henrik Zetterberg^{6

7

8

9}, Sebastian Schade¹, Roland G Gera¹⁰, Wenting Wang¹¹, Feng Gao¹¹, Mark Frasier¹², Lana M Chahine¹³, Christopher S Coffey¹⁴, Andrew B Singleton¹⁵, Tanya Simuni¹⁶, Daniel Weintraub¹⁷, John Seibyl¹⁸, Arthur W Toga¹⁹, Caroline M Tanner²⁰, Karl Kieburtz²¹, Kenneth Marek^{12

18}, Andrew Siderowf¹⁷, Jesse M Cedarbaum²², Samantha J Hutten¹², Claudia Trenkwalder², Danielle Graham²³

Affiliations

¹ Department of Neurology, University Medical Center Goettingen, Goettingen, Germany.
² Paracelsus-Elena Klinik, Kassel, Germany.
³ Department of Neuropathology, University Medical Center Goettingen, Goettingen, Germany.
⁴ Department of Neurosciences, University of California, San Diego, San Diego, California, USA.
⁵ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁶ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁷ Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
⁸ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom.
⁹ UK Dementia Research Institute at UCL, London, United Kingdom.
¹⁰ Department of Medical Statistics, University Medical Center Goettingen, Goettingen, Germany.
¹¹ Biostatistics, Biogen, Cambridge, Massachusetts, USA.
¹² The Michael J. Fox Foundation for Parkinson's Research, New York, New York, USA.
¹³ Department of Neurology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
¹⁴ Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, USA.
¹⁵ Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
¹⁶ Parkinson's Disease and Movement Disorders Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹⁷ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁸ Institute for Neurodegenerative Disorders, New Haven, Connecticut, USA.
¹⁹ Laboratory of Neuro Imaging, University of Southern California, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.
²⁰ Department of Neurology, University of California San Francisco, San Francisco, California, USA, and Parkinson's Disease Research Education and Clinical Center, San Francisco Veterans Affairs Health Care System, San Francisco, California, USA.
²¹ Clinical Trials Coordination Center, University of Rochester Medical Center, Rochester, New York, USA.
²² Coeruleus Clinical Sciences LLC, Woodbridge, Connecticut, USA.
²³ Discovery and Early Development Biomarkers, Biogen, Cambridge, Massachusetts, USA.

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. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease/parkinsonism; cohort studies; outcome research.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Cohort Studies
Disease Progression
Humans
Intermediate Filaments
Parkinson Disease*

Substances

Biomarkers

Grants and funding

Z01 AG000949/ImNIH/Intramural NIH HHS/United States