A multicentre validation study of the diagnostic value of plasma neurofilament light
(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.
(Less)
- author
- organization
- publishing date
- 2021
- 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
- 2024-11-18 13:04:15
@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}}, }