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.
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This post is Copyright: Linnemann, C., Wilke, C., Mengel, D., Zetterberg, H., Heller, C., Kuhle, J., Bouzigues, A., Russell, L. L., Foster, P. H., Ferry-Bolder, E., Van Swieten, J. C., Jiskoot, L. C., Seelaar, H., Moreno, F., Borroni, B., Sanchez-Valle, R., Galimberti, D., Laforce, R., Graff, C., Masellis, M., Tartaglia, M. C., Rowe, J. B., Finger, E., Vandenberghe, R., de Mendonca, A., Butler, C. R., Gerhard, A., Ducharme, S., Ber, I. L. E., Tiraboschi, P., Santana, I., Pasquier, F., Levin, J., Otto, M., Sorbi, S., Rohrer, J. D., Synofzik, M., GENFI, Nelson, Bocchetta, Cash, Thomas, Todd, Benotmane, Nicholas, Samra, Shafei, Timberlake, Cope, Rittman, Alberici, Premi, Gasparotti, Cantoni, Buratti, Arighi, Fenoglio, Scarpini, Fumagalli, Borracci, Rossi, Giaccone, Fede, Caroppo, Tiraboschi, Prioni, Redaelli, Tang-Wai, Rogaeva, Castelo-Branco, Freedman, Keren, Black, Mitchell, Shoesmith, Bartha, Rademakers, Poos, Papma, Giannini, Minkelen, Pijnenburg, Nacmias, Ferrari, Polito, Lombardi, Bessi, Veldsman, Andersson, Thonberg, Öijerstedt, Jelic, Thompson, Langheinrich, Llado, Antonell, Olives, Balasa, Bargallo, Borrego-Ecija, Verdelho, Maruta, Ferreira, Miltenberger, Coelho, Couto, Gabilondo, Gorostidi, Villanua, Canada, Tainta, Zulaica, Barandiaran, Alves, Bender, Graf, Vogels, Vandenbulcke, Philip, Bruffaerts, Poesen, Rosa-Neto, Gauthier, Camuzat, Brice, Bertrand, Funkiewiez, Rinaldi, Saracino, Colliot, Sayah, Prix, Wlasich, Wagemann, Loosli, Schönecker, Hoegen, Lombardi, Anderl-Straub, Rollin, Kuchcinski, Bertoux, Lebouvier, Deramecourt, Santiago, Duro, Leitao, Almeida, Tabuas-Pereira, Afonso | August 16, 2024