A multicentre validation study of the diagnostic value of plasma neurofilament light
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
|---|---|
| Enthalten in: |
Nature communications - 12(2021), 1 vom: 07. Juni, Seite 3400 |
| Sprache: |
Englisch |
|---|
| Links: |
|---|
| Themen: |
Biomarkers |
|---|
| Anmerkungen: |
Date Completed 15.06.2021 Date Revised 23.03.2022 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-021-23620-z |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM326478248 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM326478248 | ||
| 003 | DE-627 | ||
| 005 | 20231225194703.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-021-23620-z |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1088.xml |
| 035 | |a (DE-627)NLM326478248 | ||
| 035 | |a (NLM)34099648 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Ashton, Nicholas J |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A multicentre validation study of the diagnostic value of plasma neurofilament light |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 15.06.2021 | ||
| 500 | |a Date Revised 23.03.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, N.I.H., Intramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Validation Study | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Neurofilament Proteins |2 NLM | |
| 650 | 7 | |a neurofilament protein L |2 NLM | |
| 700 | 1 | |a Janelidze, Shorena |e verfasserin |4 aut | |
| 700 | 1 | |a Al Khleifat, Ahmad |e verfasserin |4 aut | |
| 700 | 1 | |a Leuzy, Antoine |e verfasserin |4 aut | |
| 700 | 1 | |a van der Ende, Emma L |e verfasserin |4 aut | |
| 700 | 1 | |a Karikari, Thomas K |e verfasserin |4 aut | |
| 700 | 1 | |a Benedet, Andrea L |e verfasserin |4 aut | |
| 700 | 1 | |a Pascoal, Tharick A |e verfasserin |4 aut | |
| 700 | 1 | |a Lleó, Alberto |e verfasserin |4 aut | |
| 700 | 1 | |a Parnetti, Lucilla |e verfasserin |4 aut | |
| 700 | 1 | |a Galimberti, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Bonanni, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Pilotto, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Padovani, Alessandro |e verfasserin |4 aut | |
| 700 | 1 | |a Lycke, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Novakova, Lenka |e verfasserin |4 aut | |
| 700 | 1 | |a Axelsson, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Velayudhan, Latha |e verfasserin |4 aut | |
| 700 | 1 | |a Rabinovici, Gil D |e verfasserin |4 aut | |
| 700 | 1 | |a Miller, Bruce |e verfasserin |4 aut | |
| 700 | 1 | |a Pariante, Carmine |e verfasserin |4 aut | |
| 700 | 1 | |a Nikkheslat, Naghmeh |e verfasserin |4 aut | |
| 700 | 1 | |a Resnick, Susan M |e verfasserin |4 aut | |
| 700 | 1 | |a Thambisetty, Madhav |e verfasserin |4 aut | |
| 700 | 1 | |a Schöll, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Fernández-Eulate, Gorka |e verfasserin |4 aut | |
| 700 | 1 | |a Gil-Bea, Francisco J |e verfasserin |4 aut | |
| 700 | 1 | |a López de Munain, Adolfo |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Chalabi, Ammar |e verfasserin |4 aut | |
| 700 | 1 | |a Rosa-Neto, Pedro |e verfasserin |4 aut | |
| 700 | 1 | |a Strydom, Andre |e verfasserin |4 aut | |
| 700 | 1 | |a Svenningsson, Per |e verfasserin |4 aut | |
| 700 | 1 | |a Stomrud, Erik |e verfasserin |4 aut | |
| 700 | 1 | |a Santillo, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Aarsland, Dag |e verfasserin |4 aut | |
| 700 | 1 | |a van Swieten, John C |e verfasserin |4 aut | |
| 700 | 1 | |a Palmqvist, Sebastian |e verfasserin |4 aut | |
| 700 | 1 | |a Zetterberg, Henrik |e verfasserin |4 aut | |
| 700 | 1 | |a Blennow, Kaj |e verfasserin |4 aut | |
| 700 | 1 | |a Hye, Abdul |e verfasserin |4 aut | |
| 700 | 1 | |a Hansson, Oskar |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 12(2021), 1 vom: 07. Juni, Seite 3400 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:12 |g year:2021 |g number:1 |g day:07 |g month:06 |g pages:3400 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-021-23620-z |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 12 |j 2021 |e 1 |b 07 |c 06 |h 3400 | ||