• Christoph Linnemann, Carlo Wilke, David Mengel, Henrik Zetterberg, Carolin Heller, Jens Kuhle, Arabella Bouzigues, Lucy L Russell, Phoebe H Foster, Eve Ferry-Bolder, John Cornelis Van Swieten, Lize C Jiskoot, Harro Seelaar, Fermin Moreno, Barbara Borroni, Raquel Sánchez-Valle, Daniela Galimberti, Robert Laforce, Caroline Graff, Mario Masellis, Maria Carmela Tartaglia, James Benedict Rowe, Elizabeth Finger, Rik Vandenberghe, Alexandre de Mendonca, Chris R Butler, Alexander Gerhard, Simon Ducharme, Isabelle L E Ber, Pietro Tiraboschi, Isabel Santana, Florence Pasquier, Johannes Levin, Markus Otto, Sandro Sorbi, Jonathan Daniel Rohrer, Matthis Synofzik, and GENFI.
• Division Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany matthis.synofzik@uni-tuebingen.de christoph.linnemann@upk.ch.
• J. Neurol. Neurosurg. Psychiatr. 2024 Aug 16; 95 (9): 822828822-828.

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.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.

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