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

Ashton, Nicholas J ; Janelidze, Shorena LU ; Al Khleifat, Ahmad ; Leuzy, Antoine LU ; van der Ende, Emma L ; Karikari, Thomas K ; Benedet, Andrea L ; Pascoal, Tharick A ; Lleó, Alberto and Parnetti, Lucilla , et al. (2021) In Nature Communications 12. p.1-12
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Age Factors, Aged, Biomarkers/cerebrospinal fluid, Cognitive Dysfunction/cerebrospinal fluid, Cohort Studies, Depression/cerebrospinal fluid, Down Syndrome/cerebrospinal fluid, False Positive Reactions, Female, Humans, Male, Middle Aged, Neurodegenerative Diseases/cerebrospinal fluid, Neurofilament Proteins/cerebrospinal fluid, Predictive Value of Tests, Reference Values, Sex Factors
in
Nature Communications
volume
12
article number
3400
pages
1 - 12
publisher
Nature Publishing Group
external identifiers
  • pmid:34099648
  • scopus:85107306441
ISSN
2041-1723
DOI
10.1038/s41467-021-23620-z
language
English
LU publication?
yes
id
c7b47565-6a88-4b98-8e2b-3ae63b1edbf0
date added to LUP
2021-11-17 18:03:10
date last changed
2024-04-20 16:36:35
@article{c7b47565-6a88-4b98-8e2b-3ae63b1edbf0,
  abstract     = {{<p>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.</p>}},
  author       = {{Ashton, Nicholas J and Janelidze, Shorena and Al Khleifat, Ahmad and Leuzy, Antoine and van der Ende, Emma L and Karikari, Thomas K and Benedet, Andrea L and Pascoal, Tharick A and Lleó, Alberto and Parnetti, Lucilla and Galimberti, Daniela and Bonanni, Laura and Pilotto, Andrea and Padovani, Alessandro and Lycke, Jan and Novakova, Lenka and Axelsson, Markus and Velayudhan, Latha and Rabinovici, Gil D and Miller, Bruce and Pariante, Carmine and Nikkheslat, Naghmeh and Resnick, Susan M and Thambisetty, Madhav and Schöll, Michael and Fernández-Eulate, Gorka and Gil-Bea, Francisco J and López de Munain, Adolfo and Al-Chalabi, Ammar and Rosa-Neto, Pedro and Strydom, Andre and Svenningsson, Per and Stomrud, Erik and Santillo, Alexander and Aarsland, Dag and van Swieten, John C and Palmqvist, Sebastian and Zetterberg, Henrik and Blennow, Kaj and Hye, Abdul and Hansson, Oskar}},
  issn         = {{2041-1723}},
  keywords     = {{Age Factors; Aged; Biomarkers/cerebrospinal fluid; Cognitive Dysfunction/cerebrospinal fluid; Cohort Studies; Depression/cerebrospinal fluid; Down Syndrome/cerebrospinal fluid; False Positive Reactions; Female; Humans; Male; Middle Aged; Neurodegenerative Diseases/cerebrospinal fluid; Neurofilament Proteins/cerebrospinal fluid; Predictive Value of Tests; Reference Values; Sex Factors}},
  language     = {{eng}},
  pages        = {{1--12}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{A multicentre validation study of the diagnostic value of plasma neurofilament light}},
  url          = {{http://dx.doi.org/10.1038/s41467-021-23620-z}},
  doi          = {{10.1038/s41467-021-23620-z}},
  volume       = {{12}},
  year         = {{2021}},
}