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

Parkinsonism Relat Disord. 2021 Jun:87:41-47. doi: 10.1016/j.parkreldis.2021.04.016. Epub 2021 Apr 27.

Authors

Andrea Pilotto¹, Alberto Imarisio², Francesca Conforti², Andrea Scalvini², Stefano Masciocchi², Sara Nocivelli², Rosanna Turrone², Stefano Gipponi², Elisabetta Cottini², Barbara Borroni², Maria Cristina Rizzetti³, Marina Pizzi⁴, Laura Bonanni⁵, Andrea Sturchio⁶, Alberto J Espay⁶, Henrik Zetterberg⁷, Nicholas J Ashton⁸, Abdul Hye⁹, Alessandro Padovani²

Affiliations

¹ Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; FERB Onlus, Ospedale S. Isidoro, Trescore Balneario, Bergamo, Italy. Electronic address: [email protected].
² Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
³ FERB Onlus, Ospedale S. Isidoro, Trescore Balneario, Bergamo, Italy.
⁴ Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
⁵ Department of Neuroscience Imaging and Clinical Sciences, University G. D'Annunzio of Chieti-Pescara, Chieti, Italy.
⁶ James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, Department of Neurology, University of Cincinnati, Cincinnati, OH, USA.
⁷ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK.
⁸ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Sweden; King's College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
⁹ King's College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.

PMID: 33964785
DOI: 10.1016/j.parkreldis.2021.04.016

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.

Publication types

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

MeSH terms

Aged
Aged, 80 and over
Cognitive Dysfunction / etiology
Disease Progression*
Female
Follow-Up Studies
Humans
Hypotension, Orthostatic / etiology
Male
Middle Aged
Neurofilament Proteins / blood*
Parkinson Disease / blood*
Parkinson Disease / classification*
Parkinson Disease / complications
Parkinson Disease / physiopathology*
Phenotype
REM Sleep Behavior Disorder / etiology

Substances

Neurofilament Proteins
neurofilament protein L