A multicentre validation study of the diagnostic value of plasma neurofilament light
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Published:2021-06-07
Issue:1
Volume:12
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Ashton Nicholas J.ORCID, Janelidze Shorena, Al Khleifat AhmadORCID, Leuzy Antoine, van der Ende Emma L., Karikari Thomas K.ORCID, Benedet Andrea L., Pascoal Tharick A., Lleó AlbertoORCID, Parnetti Lucilla, Galimberti DanielaORCID, Bonanni Laura, Pilotto Andrea, Padovani Alessandro, Lycke JanORCID, Novakova Lenka, Axelsson Markus, Velayudhan LathaORCID, Rabinovici Gil D., Miller Bruce, Pariante CarmineORCID, Nikkheslat Naghmeh, Resnick Susan M., Thambisetty Madhav, Schöll MichaelORCID, Fernández-Eulate GorkaORCID, Gil-Bea Francisco J., López de Munain Adolfo, Al-Chalabi AmmarORCID, Rosa-Neto Pedro, Strydom Andre, Svenningsson Per, Stomrud Erik, Santillo Alexander, Aarsland Dag, van Swieten John C., Palmqvist SebastianORCID, Zetterberg HenrikORCID, Blennow KajORCID, Hye Abdul, Hansson OskarORCID
Abstract
AbstractIncreased 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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