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. 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: pilottoandreae@gmail.com. 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.
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.
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.
Authors: Dag Aarsland; Lucia Batzu; Glenda M Halliday; Gert J Geurtsen; Clive Ballard; K Ray Chaudhuri; Daniel Weintraub Journal: Nat Rev Dis Primers Date: 2021-07-01 Impact factor: 52.329
Authors: Dorota Koníčková; Kateřina Menšíková; Lucie Tučková; Eva Hényková; Miroslav Strnad; David Friedecký; David Stejskal; Radoslav Matěj; Petr Kaňovský Journal: Biomedicines Date: 2022-07-21
Authors: Charity G Patterson; Elizabeth Joslin; Alexandra B Gil; Wendy Spigle; Todd Nemet; Lana Chahine; Cory L Christiansen; Ed Melanson; Wendy M Kohrt; Martina Mancini; Deborah Josbeno; Katherine Balfany; Garett Griffith; Mac Kenzie Dunlap; Guillaume Lamotte; Erin Suttman; Danielle Larson; Chantale Branson; Kathleen E McKee; Li Goelz; Cynthia Poon; Barbara Tilley; Un Jung Kang; Malú Gámez Tansey; Nijee Luthra; Caroline M Tanner; Jacob M Haus; Giamila Fantuzzi; Nikolaus R McFarland; Paulina Gonzalez-Latapi; Tatiana Foroud; Robert Motl; Michael A Schwarzschild; Tanya Simuni; Kenneth Marek; Anna Naito; Codrin Lungu; Daniel M Corcos Journal: Trials Date: 2022-10-06 Impact factor: 2.728