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 MillerCarmine 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, Oskar Hansson

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233 Citations (Scopus)


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.

Original languageEnglish
Article number3400
JournalNature Communications
Issue number1
Publication statusPublished - 7 Jun 2021


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