BackgroundBlood 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.MethodsComparative 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.ResultsNfL 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.ConclusionsOur 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.

NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD: a large GENFI study / C. Linnemann, C. Wilke, D. Mengel, H. Zetterberg, C. Heller, J. Kuhle, A. Bouzigues, L.L. Russell, P.H. Foster, E. Ferry-Bolder, J.C. Van Swieten, L.C. Jiskoot, H. Seelaar, F. Moreno, B. Borroni, R. Sánchez-Valle, D. Galimberti, R. Laforce, C. Graff, M. Masellis, M.C. Tartaglia, J.B. Rowe, E. Finger, R. Vandenberghe, A. de Mendonca, C.R. Butler, A. Gerhard, S. Ducharme, I.L.E. Ber, P. Tiraboschi, I. Santana, F. Pasquier, J. Levin, M. Otto, S. Sorbi, J.D. Rohrer, M. Synofzik. - In: JOURNAL OF NEUROLOGY, NEUROSURGERY AND PSYCHIATRY. - ISSN 0022-3050. - (2024), pp. jnnp-2023-332464.1-jnnp-2023-332464.7. [Epub ahead of print] [10.1136/jnnp-2023-332464]

NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD: a large GENFI study

D. Galimberti;
2024

Abstract

BackgroundBlood 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.MethodsComparative 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.ResultsNfL 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.ConclusionsOur 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.
COGNITION; FRONTOTEMPORAL DEMENTIA; NEUROPSYCHIATRY;
Settore BIO/13 - Biologia Applicata
   Fluid Biomarkers for Neurodegenerative Dementias
   FLUBIODEM
   European Commission
   Horizon Europe Framework Programme
   101053962

   Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis
   MIRIADE
   European Commission
   Horizon 2020 Framework Programme
   860197
2024
19-gen-2024
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/1059308
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