Plasma NfL, clinical subtypes and motor progression in Parkinson's disease

Andrea Pilotto; Alberto Imarisio; Francesca Conforti; Andrea Scalvini; Stefano Masciocchi; Sara Nocivelli; Rosanna Turrone; Stefano Gipponi; Elisabetta Cottini; Barbara Borroni; Maria Cristina Rizzetti; Marina Pizzi; Laura Bonanni; Andrea Sturchio; Alberto J. Espay; Henrik Zetterberg; Nicholas J. Ashton; Abdul Hye; Alessandro Padovani

doi:10.1016/j.parkreldis.2021.04.016

Plasma NfL, clinical subtypes and motor progression in Parkinson's disease

Andrea Pilotto^*, Alberto Imarisio, Francesca Conforti, Andrea Scalvini, Stefano Masciocchi, Sara Nocivelli, Rosanna Turrone, Stefano Gipponi, Elisabetta Cottini, Barbara Borroni, Maria Cristina Rizzetti, Marina Pizzi, Laura Bonanni, Andrea Sturchio, Alberto J. Espay, Henrik Zetterberg, Nicholas J. Ashton, Abdul Hye, Alessandro Padovani

^*Corresponding author for this work

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

41 Citations (Scopus)

Abstract

Introduction: neurofilament light chain (NfL) levels have been proposed as reliable biomarkers of neurodegeneration in Parkinson's disease (PD) but the relationship between plasma NfL, clinical subtypes of PD and motor progression is still debated. Methods: plasma NfL concentration was measured in 45 healthy controls and consecutive 92 PD patients who underwent an extensive motor and non-motor assessment at baseline and after 2 years of follow-up. PD malignant phenotype was defined as the combination of at least two out of cognitive impairment, orthostatic hypotension and REM sleep behavior disorder. PD patients were divided according to the age-adjusted cut-offs of plasma NfL levels into high and normal NfL (H-NfL and N-NfL, respectively). A multivariable linear regression model was used to assess the value of plasma NfL as predictor of 2-years progression in PD. Results: NfL was higher in PD patients than in controls (p = 0.037). H-NfL (n = 16) group exhibited more severe motor and non-motor symptoms, higher prevalence of malignant phenotype and worse motor progression (MDS-UPDRS-III 11.3 vs 0.7 points, p = 0.003) compared to N-NfL group (n = 76). In linear regression analyses plasma NfL emerged as the best predictor of 2-year motor progression compared to age, sex, disease duration, baseline motor/non-motor variables. Conclusion: increased plasma NfL concentration is associated with malignant PD phenotype and faster motor progression. These findings support the role of NfL assessment as a useful measure for stratifying patients with different baseline slopes of decline in future clinical trials of putative disease-modifying treatments.

Original language	English
Pages (from-to)	41-47
Number of pages	7
Journal	Parkinsonism and Related Disorders
Volume	87
DOIs	https://doi.org/10.1016/j.parkreldis.2021.04.016
Publication status	Published - Jun 2021

Keywords

Biomarkers
Neurofilament light chain
Parkinson's disease
Phenotypes
Progression

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10.1016/j.parkreldis.2021.04.016

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Pilotto, A., Imarisio, A., Conforti, F., Scalvini, A., Masciocchi, S., Nocivelli, S., Turrone, R., Gipponi, S., Cottini, E., Borroni, B., Rizzetti, M. C., Pizzi, M., Bonanni, L., Sturchio, A., Espay, A. J., Zetterberg, H., Ashton, N. J., Hye, A., & Padovani, A. (2021). Plasma NfL, clinical subtypes and motor progression in Parkinson's disease. Parkinsonism and Related Disorders, 87, 41-47. https://doi.org/10.1016/j.parkreldis.2021.04.016

@article{edff7896fc15498b867867772e573300,

title = "Plasma NfL, clinical subtypes and motor progression in Parkinson's disease",

abstract = "Introduction: neurofilament light chain (NfL) levels have been proposed as reliable biomarkers of neurodegeneration in Parkinson's disease (PD) but the relationship between plasma NfL, clinical subtypes of PD and motor progression is still debated. Methods: plasma NfL concentration was measured in 45 healthy controls and consecutive 92 PD patients who underwent an extensive motor and non-motor assessment at baseline and after 2 years of follow-up. PD malignant phenotype was defined as the combination of at least two out of cognitive impairment, orthostatic hypotension and REM sleep behavior disorder. PD patients were divided according to the age-adjusted cut-offs of plasma NfL levels into high and normal NfL (H-NfL and N-NfL, respectively). A multivariable linear regression model was used to assess the value of plasma NfL as predictor of 2-years progression in PD. Results: NfL was higher in PD patients than in controls (p = 0.037). H-NfL (n = 16) group exhibited more severe motor and non-motor symptoms, higher prevalence of malignant phenotype and worse motor progression (MDS-UPDRS-III 11.3 vs 0.7 points, p = 0.003) compared to N-NfL group (n = 76). In linear regression analyses plasma NfL emerged as the best predictor of 2-year motor progression compared to age, sex, disease duration, baseline motor/non-motor variables. Conclusion: increased plasma NfL concentration is associated with malignant PD phenotype and faster motor progression. These findings support the role of NfL assessment as a useful measure for stratifying patients with different baseline slopes of decline in future clinical trials of putative disease-modifying treatments.",

keywords = "Biomarkers, Neurofilament light chain, Parkinson's disease, Phenotypes, Progression",

author = "Andrea Pilotto and Alberto Imarisio and Francesca Conforti and Andrea Scalvini and Stefano Masciocchi and Sara Nocivelli and Rosanna Turrone and Stefano Gipponi and Elisabetta Cottini and Barbara Borroni and Rizzetti, {Maria Cristina} and Marina Pizzi and Laura Bonanni and Andrea Sturchio and Espay, {Alberto J.} and Henrik Zetterberg and Ashton, {Nicholas J.} and Abdul Hye and Alessandro Padovani",

note = "Funding Information: The recruitment of patients was partially supported by BIOMANE Project from the Health and Wealth research grants 2016 of the University of Brescia [grant number NP 1471, DMA]. Funding Information: Alberto Espay has received grant support from the NIH and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, Neuroderm, Neurocrine, Amneal, Adamas, Acadia, Acorda, Kyowa Kirin, Sunovion, Lundbeck, and USWorldMeds; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer; and honoraria from USWorldMeds, Acadia, and Sunovion. Funding Information: Laura Bonanni received unrelated national grants from the Italian Ministry of Health, from European Commission (PD MIND project, IMI call) and from Mentis cura, Oslo srl; fees from G.E. Healthcare for teaching courses. Served as reviewer for NIHhas no financial conflicts to disclose. Publisher Copyright: {\textcopyright} 2021 Elsevier Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = jun,

doi = "10.1016/j.parkreldis.2021.04.016",

language = "English",

volume = "87",

pages = "41--47",

journal = "Parkinsonism and Related Disorders",

issn = "1353-8020",

publisher = "Elsevier",

}

Pilotto, A, Imarisio, A, Conforti, F, Scalvini, A, Masciocchi, S, Nocivelli, S, Turrone, R, Gipponi, S, Cottini, E, Borroni, B, Rizzetti, MC, Pizzi, M, Bonanni, L, Sturchio, A, Espay, AJ, Zetterberg, H, Ashton, NJ , Hye, A & Padovani, A 2021, 'Plasma NfL, clinical subtypes and motor progression in Parkinson's disease', Parkinsonism and Related Disorders, vol. 87, pp. 41-47. https://doi.org/10.1016/j.parkreldis.2021.04.016

TY - JOUR

T1 - Plasma NfL, clinical subtypes and motor progression in Parkinson's disease

AU - Pilotto, Andrea

AU - Imarisio, Alberto

AU - Conforti, Francesca

AU - Scalvini, Andrea

AU - Masciocchi, Stefano

AU - Nocivelli, Sara

AU - Turrone, Rosanna

AU - Gipponi, Stefano

AU - Cottini, Elisabetta

AU - Borroni, Barbara

AU - Rizzetti, Maria Cristina

AU - Pizzi, Marina

AU - Bonanni, Laura

AU - Sturchio, Andrea

AU - Espay, Alberto J.

AU - Zetterberg, Henrik

AU - Ashton, Nicholas J.

AU - Hye, Abdul

AU - Padovani, Alessandro

N1 - Funding Information: The recruitment of patients was partially supported by BIOMANE Project from the Health and Wealth research grants 2016 of the University of Brescia [grant number NP 1471, DMA]. Funding Information: Alberto Espay has received grant support from the NIH and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Abbvie, Neuroderm, Neurocrine, Amneal, Adamas, Acadia, Acorda, Kyowa Kirin, Sunovion, Lundbeck, and USWorldMeds; publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press, and Springer; and honoraria from USWorldMeds, Acadia, and Sunovion. Funding Information: Laura Bonanni received unrelated national grants from the Italian Ministry of Health, from European Commission (PD MIND project, IMI call) and from Mentis cura, Oslo srl; fees from G.E. Healthcare for teaching courses. Served as reviewer for NIHhas no financial conflicts to disclose. Publisher Copyright: © 2021 Elsevier Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/6

Y1 - 2021/6

N2 - Introduction: neurofilament light chain (NfL) levels have been proposed as reliable biomarkers of neurodegeneration in Parkinson's disease (PD) but the relationship between plasma NfL, clinical subtypes of PD and motor progression is still debated. Methods: plasma NfL concentration was measured in 45 healthy controls and consecutive 92 PD patients who underwent an extensive motor and non-motor assessment at baseline and after 2 years of follow-up. PD malignant phenotype was defined as the combination of at least two out of cognitive impairment, orthostatic hypotension and REM sleep behavior disorder. PD patients were divided according to the age-adjusted cut-offs of plasma NfL levels into high and normal NfL (H-NfL and N-NfL, respectively). A multivariable linear regression model was used to assess the value of plasma NfL as predictor of 2-years progression in PD. Results: NfL was higher in PD patients than in controls (p = 0.037). H-NfL (n = 16) group exhibited more severe motor and non-motor symptoms, higher prevalence of malignant phenotype and worse motor progression (MDS-UPDRS-III 11.3 vs 0.7 points, p = 0.003) compared to N-NfL group (n = 76). In linear regression analyses plasma NfL emerged as the best predictor of 2-year motor progression compared to age, sex, disease duration, baseline motor/non-motor variables. Conclusion: increased plasma NfL concentration is associated with malignant PD phenotype and faster motor progression. These findings support the role of NfL assessment as a useful measure for stratifying patients with different baseline slopes of decline in future clinical trials of putative disease-modifying treatments.

AB - Introduction: neurofilament light chain (NfL) levels have been proposed as reliable biomarkers of neurodegeneration in Parkinson's disease (PD) but the relationship between plasma NfL, clinical subtypes of PD and motor progression is still debated. Methods: plasma NfL concentration was measured in 45 healthy controls and consecutive 92 PD patients who underwent an extensive motor and non-motor assessment at baseline and after 2 years of follow-up. PD malignant phenotype was defined as the combination of at least two out of cognitive impairment, orthostatic hypotension and REM sleep behavior disorder. PD patients were divided according to the age-adjusted cut-offs of plasma NfL levels into high and normal NfL (H-NfL and N-NfL, respectively). A multivariable linear regression model was used to assess the value of plasma NfL as predictor of 2-years progression in PD. Results: NfL was higher in PD patients than in controls (p = 0.037). H-NfL (n = 16) group exhibited more severe motor and non-motor symptoms, higher prevalence of malignant phenotype and worse motor progression (MDS-UPDRS-III 11.3 vs 0.7 points, p = 0.003) compared to N-NfL group (n = 76). In linear regression analyses plasma NfL emerged as the best predictor of 2-year motor progression compared to age, sex, disease duration, baseline motor/non-motor variables. Conclusion: increased plasma NfL concentration is associated with malignant PD phenotype and faster motor progression. These findings support the role of NfL assessment as a useful measure for stratifying patients with different baseline slopes of decline in future clinical trials of putative disease-modifying treatments.

KW - Biomarkers

KW - Neurofilament light chain

KW - Parkinson's disease

KW - Phenotypes

KW - Progression

UR - http://www.scopus.com/inward/record.url?scp=85105265322&partnerID=8YFLogxK

U2 - 10.1016/j.parkreldis.2021.04.016

DO - 10.1016/j.parkreldis.2021.04.016

M3 - Article

AN - SCOPUS:85105265322

SN - 1353-8020

VL - 87

SP - 41

EP - 47

JO - Parkinsonism and Related Disorders

JF - Parkinsonism and Related Disorders

ER -

Plasma NfL, clinical subtypes and motor progression in Parkinson's disease

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Keywords

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