NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD : a large GENFI study
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ..
BACKGROUND: Blood neurofilament light chain (NfL) is increasingly considered as a key trial biomarker in genetic frontotemporal dementia (gFTD). We aimed to facilitate the use of NfL in gFTD multicentre trials by testing its (1) reliability across labs; (2) reliability to stratify gFTD disease stages; (3) comparability between blood matrices and (4) stability across recruiting sites.
METHODS: Comparative analysis of blood NfL levels in a large gFTD cohort (GENFI) for (1)-(4), with n=344 samples (n=148 presymptomatic, n=11 converter, n=46 symptomatic subjects, with mutations in C9orf72, GRN or MAPT; and n=139 within-family controls), each measured in three different international labs by Simoa HD-1 analyzer.
RESULTS: NfL revealed an excellent consistency (intraclass correlation coefficient (ICC) 0.964) and high reliability across the three labs (maximal bias (pg/mL) in Bland-Altman analysis: 1.12±1.20). High concordance of NfL across laboratories was moreover reflected by high areas under the curve for discriminating conversion stage against the (non-converting) presymptomatic stage across all three labs. Serum and plasma NfL were largely comparable (ICC 0.967). The robustness of NfL across 13 recruiting sites was demonstrated by a linear mixed effect model.
CONCLUSIONS: Our results underline the suitability of blood NfL in gFTD multicentre trials, including cross-lab reliable stratification of the highly trial-relevant conversion stage, matrix comparability and cross-site robustness.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Journal of neurology, neurosurgery, and psychiatry - (2024) vom: 01. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Linnemann, Christoph [VerfasserIn] |
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COGNITION |
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| Anmerkungen: |
Date Revised 13.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1136/jnnp-2023-332464 |
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| 100 | 1 | |a Linnemann, Christoph |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD |b a large GENFI study |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ. | ||
| 520 | |a BACKGROUND: Blood neurofilament light chain (NfL) is increasingly considered as a key trial biomarker in genetic frontotemporal dementia (gFTD). We aimed to facilitate the use of NfL in gFTD multicentre trials by testing its (1) reliability across labs; (2) reliability to stratify gFTD disease stages; (3) comparability between blood matrices and (4) stability across recruiting sites | ||
| 520 | |a METHODS: Comparative analysis of blood NfL levels in a large gFTD cohort (GENFI) for (1)-(4), with n=344 samples (n=148 presymptomatic, n=11 converter, n=46 symptomatic subjects, with mutations in C9orf72, GRN or MAPT; and n=139 within-family controls), each measured in three different international labs by Simoa HD-1 analyzer | ||
| 520 | |a RESULTS: NfL revealed an excellent consistency (intraclass correlation coefficient (ICC) 0.964) and high reliability across the three labs (maximal bias (pg/mL) in Bland-Altman analysis: 1.12±1.20). High concordance of NfL across laboratories was moreover reflected by high areas under the curve for discriminating conversion stage against the (non-converting) presymptomatic stage across all three labs. Serum and plasma NfL were largely comparable (ICC 0.967). The robustness of NfL across 13 recruiting sites was demonstrated by a linear mixed effect model | ||
| 520 | |a CONCLUSIONS: Our results underline the suitability of blood NfL in gFTD multicentre trials, including cross-lab reliable stratification of the highly trial-relevant conversion stage, matrix comparability and cross-site robustness | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a COGNITION | |
| 650 | 4 | |a FRONTOTEMPORAL DEMENTIA | |
| 650 | 4 | |a NEUROPSYCHIATRY | |
| 700 | 1 | |a Wilke, Carlo |e verfasserin |4 aut | |
| 700 | 1 | |a Mengel, David |e verfasserin |4 aut | |
| 700 | 1 | |a Zetterberg, Henrik |e verfasserin |4 aut | |
| 700 | 1 | |a Heller, Carolin |e verfasserin |4 aut | |
| 700 | 1 | |a Kuhle, Jens |e verfasserin |4 aut | |
| 700 | 1 | |a Bouzigues, Arabella |e verfasserin |4 aut | |
| 700 | 1 | |a Russell, Lucy L |e verfasserin |4 aut | |
| 700 | 1 | |a Foster, Phoebe H |e verfasserin |4 aut | |
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| 700 | 1 | |a Van Swieten, John Cornelis |e verfasserin |4 aut | |
| 700 | 1 | |a Jiskoot, Lize C |e verfasserin |4 aut | |
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| 700 | 1 | |a Borroni, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Sánchez-Valle, Raquel |e verfasserin |4 aut | |
| 700 | 1 | |a Galimberti, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Laforce, Robert |c Jr |e verfasserin |4 aut | |
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| 700 | 1 | |a Tartaglia, Maria Carmela |e verfasserin |4 aut | |
| 700 | 1 | |a Rowe, James Benedict |e verfasserin |4 aut | |
| 700 | 1 | |a Finger, Elizabeth |e verfasserin |4 aut | |
| 700 | 1 | |a Vandenberghe, Rik |e verfasserin |4 aut | |
| 700 | 1 | |a de Mendonca, Alexandre |e verfasserin |4 aut | |
| 700 | 1 | |a Butler, Chris R |e verfasserin |4 aut | |
| 700 | 1 | |a Gerhard, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Ducharme, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a Ber, Isabelle L E |e verfasserin |4 aut | |
| 700 | 1 | |a Tiraboschi, Pietro |e verfasserin |4 aut | |
| 700 | 1 | |a Santana, Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Pasquier, Florence |e verfasserin |4 aut | |
| 700 | 1 | |a Levin, Johannes |e verfasserin |4 aut | |
| 700 | 1 | |a Otto, Markus |e verfasserin |4 aut | |
| 700 | 1 | |a Sorbi, Sandro |e verfasserin |4 aut | |
| 700 | 1 | |a Rohrer, Jonathan Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Synofzik, Matthis |e verfasserin |4 aut | |
| 700 | 0 | |a GENFI |e verfasserin |4 aut | |
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| 700 | 1 | |a Nicholas, Jennifer |e investigator |4 oth | |
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| 700 | 1 | |a Shafei, Rachelle |e investigator |4 oth | |
| 700 | 1 | |a Timberlake, Carolyn |e investigator |4 oth | |
| 700 | 1 | |a Cope, Thomas |e investigator |4 oth | |
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| 700 | 1 | |a Alberici, Antonella |e investigator |4 oth | |
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| 700 | 1 | |a Gasparotti, Roberto |e investigator |4 oth | |
| 700 | 1 | |a Cantoni, Valentina |e investigator |4 oth | |
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| 700 | 1 | |a Arighi, Andrea |e investigator |4 oth | |
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| 700 | 1 | |a Rogaeva, Ekaterina |e investigator |4 oth | |
| 700 | 1 | |a Castelo-Branco, Miguel |e investigator |4 oth | |
| 700 | 1 | |a Freedman, Morris |e investigator |4 oth | |
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