A multicentre validation study of the diagnostic value of plasma neurofilament light

Nicholas J. Ashton (), Shorena Janelidze, Ahmad Al Khleifat, Antoine Leuzy, Emma L. van der Ende, Thomas K. Karikari, Andrea L. Benedet, Tharick A. Pascoal, Alberto Lleó, Lucilla Parnetti, Daniela Galimberti, Laura Bonanni, Andrea Pilotto, Alessandro Padovani, Jan Lycke, Lenka Novakova, Markus Axelsson, Latha Velayudhan, Gil D. Rabinovici, Bruce Miller, Carmine Pariante, Naghmeh Nikkheslat, Susan M. Resnick, Madhav Thambisetty, Michael Schöll, Gorka Fernández-Eulate, Francisco J. Gil-Bea, Adolfo López de Munain, Ammar Al-Chalabi, Pedro Rosa-Neto, Andre Strydom, Per Svenningsson, Erik Stomrud, Alexander Santillo, Dag Aarsland, John C. van Swieten, Sebastian Palmqvist, Henrik Zetterberg, Kaj Blennow, Abdul Hye and Oskar Hansson ()
Additional contact information
Nicholas J. Ashton: The Sahlgrenska Academy at the University of Gothenburg
Shorena Janelidze: Lund University
Ahmad Al Khleifat: Maurice Wohl Clinical Neuroscience Institute, King’s College London
Antoine Leuzy: Lund University
Emma L. van der Ende: Erasmus University Medical Center
Thomas K. Karikari: The Sahlgrenska Academy at the University of Gothenburg
Andrea L. Benedet: The McGill University Research Centre for Studies in Aging
Tharick A. Pascoal: The McGill University Research Centre for Studies in Aging
Alberto Lleó: Hospital de la Santa Creu i Sant Pau
Lucilla Parnetti: University of Perugia
Daniela Galimberti: Ospedale Policlinico
Laura Bonanni: University G.d’Annunzio of Chieti-Pescara
Andrea Pilotto: University of Brescia
Alessandro Padovani: University of Brescia
Jan Lycke: University of Gothenburg
Lenka Novakova: University of Gothenburg
Markus Axelsson: University of Gothenburg
Latha Velayudhan: King’s College London
Gil D. Rabinovici: University of California San Francisco, Memory and Aging Center
Bruce Miller: University of California San Francisco, Memory and Aging Center
Carmine Pariante: King’s College London
Naghmeh Nikkheslat: King’s College London
Susan M. Resnick: National Institutes of Health
Madhav Thambisetty: National Institutes of Health
Michael Schöll: The Sahlgrenska Academy at the University of Gothenburg
Gorka Fernández-Eulate: Biodonostia Health Research Institute
Francisco J. Gil-Bea: Biodonostia Health Research Institute
Adolfo López de Munain: Biodonostia Health Research Institute
Ammar Al-Chalabi: Maurice Wohl Clinical Neuroscience Institute, King’s College London
Pedro Rosa-Neto: The McGill University Research Centre for Studies in Aging
Andre Strydom: King’s College London
Per Svenningsson: King’s College London
Erik Stomrud: Lund University
Alexander Santillo: Lund University
Dag Aarsland: King’s College London
John C. van Swieten: Erasmus University Medical Center
Sebastian Palmqvist: Lund University
Henrik Zetterberg: The Sahlgrenska Academy at the University of Gothenburg
Kaj Blennow: The Sahlgrenska Academy at the University of Gothenburg
Abdul Hye: King’s College London
Oskar Hansson: Lund University

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King’s College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.

Date: 2021
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DOI: 10.1038/s41467-021-23620-z

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