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

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  • Nicholas J. Ashton

    (The Sahlgrenska Academy at the University of Gothenburg
    University of Gothenburg
    King’s College London
    NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation)

  • 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
    Montreal Neurological Institute)

  • Tharick A. Pascoal

    (The McGill University Research Centre for Studies in Aging
    Montreal Neurological Institute)

  • Alberto Lleó

    (Hospital de la Santa Creu i Sant Pau
    Instituto de Salud Carlos III)

  • Lucilla Parnetti

    (University of Perugia)

  • Daniela Galimberti

    (Ospedale Policlinico
    University of Milan)

  • Laura Bonanni

    (University G.d’Annunzio of Chieti-Pescara)

  • Andrea Pilotto

    (University of Brescia
    Parkinson’s Disease Rehabilitation Centre, FERB ONLUS)

  • Alessandro Padovani

    (University of Brescia)

  • Jan Lycke

    (University of Gothenburg
    Sahlgrenska University Hospital)

  • Lenka Novakova

    (University of Gothenburg
    Sahlgrenska University Hospital)

  • Markus Axelsson

    (University of Gothenburg
    Sahlgrenska University Hospital)

  • Latha Velayudhan

    (King’s College London
    University of Leicester)

  • Gil D. Rabinovici

    (University of California San Francisco, Memory and Aging Center
    University of California)

  • 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
    University of Gothenburg
    University College London)

  • Gorka Fernández-Eulate

    (Biodonostia Health Research Institute
    Donostia University Hospital, Osakidetza)

  • Francisco J. Gil-Bea

    (Biodonostia Health Research Institute
    Carlos III Health Institute)

  • Adolfo López de Munain

    (Biodonostia Health Research Institute
    Donostia University Hospital, Osakidetza
    Carlos III Health Institute
    Basque Country University)

  • Ammar Al-Chalabi

    (Maurice Wohl Clinical Neuroscience Institute, King’s College London
    King’s College Hospital)

  • Pedro Rosa-Neto

    (The McGill University Research Centre for Studies in Aging
    Montreal Neurological Institute)

  • Andre Strydom

    (King’s College London
    South London and Maudsley NHS Foundation Trust
    London Down Syndrome Consortium (LonDowns))

  • Per Svenningsson

    (King’s College London
    Karolinska Institutet)

  • Erik Stomrud

    (Lund University
    Skåne University Hospital)

  • Alexander Santillo

    (Lund University)

  • Dag Aarsland

    (King’s College London
    NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation
    Stavanger University Hospital)

  • John C. van Swieten

    (Erasmus University Medical Center)

  • Sebastian Palmqvist

    (Lund University
    Skåne University Hospital, Lund University)

  • Henrik Zetterberg

    (The Sahlgrenska Academy at the University of Gothenburg
    University College London
    Sahlgrenska University Hospital
    University College London)

  • Kaj Blennow

    (The Sahlgrenska Academy at the University of Gothenburg
    Sahlgrenska University Hospital)

  • Abdul Hye

    (King’s College London
    NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation
    Stavanger University Hospital)

  • Oskar Hansson

    (Lund University
    Skåne University Hospital)

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.

Suggested Citation

  • 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 & Dani, 2021. "A multicentre validation study of the diagnostic value of plasma neurofilament light," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23620-z
    DOI: 10.1038/s41467-021-23620-z
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    Cited by:

    1. Meghan Lee Arnold & Jason Cooper & Rebecca Androwski & Sohil Ardeshna & Ilija Melentijevic & Joelle Smart & Ryan J. Guasp & Ken C. Q. Nguyen & Ge Bai & David H. Hall & Barth D. Grant & Monica Driscoll, 2023. "Intermediate filaments associate with aggresome-like structures in proteostressed C. elegans neurons and influence large vesicle extrusions as exophers," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Fernando Gonzalez-Ortiz & Bjørn-Eivind Kirsebom & José Contador & Jordan E. Tanley & Per Selnes & Berglind Gísladóttir & Lene Pålhaugen & Mathilde Suhr Hemminghyth & Jonas Jarholm & Ragnhild Skogseth , 2024. "Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer’s disease," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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