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

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

Neurology

Research output: Contribution to journal › Article › peer-review

128 Scopus citations

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 language	English (US)
Pages (from-to)	1999-2008
Number of pages	10
Journal	Movement Disorders
Volume	35
Issue number	11
DOIs	https://doi.org/10.1002/mds.28206
State	Published - Nov 2020

Funding

K.K. serves as consultant for Clintrex LLC, Roche/Genentech, Novartis, Blackfynn and has grant support from NIH (NINDS, NCATS), Michael J Fox Foundation; ownership in Clintrex LLC, Hoover Brown LLC, Safe Therapeutics LLC We thank the Michael J. Fox Foundation, all of our PPMI colleagues and the many individuals who have given their time and of themselves to be participants in this study. This study was funded by The Michael J. Fox Foundation for Parkinson's Research and funding partners including Abbvie, Allergan, Avid Radiopharmaceuticals, Abbott, Biogen Inc, BioLegend, Bristol-Myers Squibb, Celgene, Denali, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Prevail Therapeutics, F. Hoffman-La Roche Ltd., Sanofi Genzyme, Servier, Takeda, Teva, UCB. Open access funding enabled and organized by Projekt DEAL. C.M.T. is an employee of the University of California \u2013 San Francisco and the San Francisco Veterans Affairs Health Care System. She receives grants from the Michael J. Fox Foundation, the Parkinson\u2019s Foundation, the Department of Defense, BioElectron, Roche/Genentech, Biogen Idec, and the National Institutes of Health, compensation for serving on Data Monitoring Committees from Biotie Therapeutics, Voyager Therapeutics, and Intec Pharma, and personal fees for consulting from Neurocrine Biosciences, Adamas Therapeutics, Biogen Idec, 23andMe, Alexza, Grey Matter, Acorda, Acadia, and CNS Ratings. T.S. has served as a consultant for Acadia, AbbVie, Adamas, Anavex, Aptinyx, Allergan, Accorda, Denali, Neuroderm, Neurocrine, Revance, Sanofi, Sunovion, TEVA, Takeda, Voyager, US World Meds, Parkinson\u2019s Foundation, and the Michael J. Fox Foundation for Parkinson\u2019s Research; Dr. Simuni has served as a speaker and received an honorarium from Acadia, Adamas, and TEVA; Dr. Simuni is on the scientific advisory board for Neuroderm, Sanofi, and MJFF. Dr. Simuni has received research funding from the NINDS, Parkinson\u2019s Foundation, MJFF, Biogen, Roche, Neuroderm, Sanofi, Sun Pharma. S.S. has received salaries from the EU Horizon 2020 research and innovation program under grant agreement No. 634821 and from the Deutsche Forschungsgemeinschaft (DFG) under grant agreement No. MO 2088/5\u20101. L.C. receives research support from the Michael J Fox Foundation, has received travel payment from MJFF to MJFF conferences, is a paid consultant to MJFF, receives research support from the UPMC Competitive Medical Research Fund, is study site investigator for a study sponsored by Biogen, is a site subinvestigator for a study sponsored by Voyager, received payment from Elsevier (for book authorship), and receives royalties from Wolters Kluwel (for book authorship). C.T. has received grants from the M.J. Fox, European grant: program Horizon 2020, and consulting fees from Britannia, Roche as well as honoraria from UCB, Gruenenthal, Otsuka. Book for PD patients (Schattauer publisher), PDSS2 Scale, European patent on Dyskinesias of PD, and no commercial interests. D.G. is supported by NIH grant AGO5131, and by the Michael J. Fox Foundation. He has provided consultation for vTv Pharmaceuticals, Eli Lilly, Inc, and Proclara, Inc.

Keywords

Parkinson's disease/parkinsonism
cohort studies
outcome research

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/mds.28206

Cite this

Mollenhauer, B., Dakna, M., Kruse, N., Galasko, D., Foroud, T., Zetterberg, H., Schade, S., Gera, R. G., Wang, W., Gao, F., Frasier, M., Chahine, L. M., Coffey, C. S., Singleton, A. B., Simuni, T., Weintraub, D., Seibyl, J., Toga, A. W., Tanner, C. M., ... Graham, D. (2020). Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson's Disease Progression. Movement Disorders, 35(11), 1999-2008. https://doi.org/10.1002/mds.28206

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title = "Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson's Disease Progression",

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.",

keywords = "Parkinson's disease/parkinsonism, cohort studies, outcome research",

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

note = "Publisher Copyright: {\textcopyright} 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.",

year = "2020",

month = nov,

doi = "10.1002/mds.28206",

language = "English (US)",

volume = "35",

pages = "1999--2008",

journal = "Movement Disorders",

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Mollenhauer, B, Dakna, M, Kruse, N, Galasko, D, Foroud, T, Zetterberg, H, Schade, S, Gera, RG, Wang, W, Gao, F, Frasier, M, Chahine, LM, Coffey, CS, Singleton, AB, Simuni, T, Weintraub, D, Seibyl, J, Toga, AW, Tanner, CM, Kieburtz, K, Marek, K, Siderowf, A, Cedarbaum, JM, Hutten, SJ, Trenkwalder, C & Graham, D 2020, 'Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson's Disease Progression', Movement Disorders, vol. 35, no. 11, pp. 1999-2008. https://doi.org/10.1002/mds.28206

TY - JOUR

T1 - Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson's Disease Progression

AU - Mollenhauer, Brit

AU - Dakna, Mohammed

AU - Kruse, Niels

AU - Galasko, Douglas

AU - Foroud, Tatiana

AU - Zetterberg, Henrik

AU - Schade, Sebastian

AU - Gera, Roland G.

AU - Wang, Wenting

AU - Gao, Feng

AU - Frasier, Mark

AU - Chahine, Lana M.

AU - Coffey, Christopher S.

AU - Singleton, Andrew B.

AU - Simuni, Tanya

AU - Weintraub, Daniel

AU - Seibyl, John

AU - Toga, Arthur W.

AU - Tanner, Caroline M.

AU - Kieburtz, Karl

AU - Marek, Kenneth

AU - Siderowf, Andrew

AU - Cedarbaum, Jesse M.

AU - Hutten, Samantha J.

AU - Trenkwalder, Claudia

AU - Graham, Danielle

PY - 2020/11

Y1 - 2020/11

N2 - 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.

AB - 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.

KW - Parkinson's disease/parkinsonism

KW - cohort studies

KW - outcome research

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JO - Movement Disorders

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ER -

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

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