Publications & Posters

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

Journal of Neurology, Neurosurgery & Psychiatry | January 19, 2024

Linnemann C, Wilke C, Mengel D, Zetterberg H, Heller C, Kuhle J, Bouzigues A, Russell LL, Foster PH, Ferry-Bolder E, Van Swieten JC, Jiskoot LC, Seelaar H, Moreno F, Borroni B, Sánchez-Valle R, Galimberti D, Laforce R Jr, Graff C, Masellis M, Tartaglia MC, Rowe JB, Finger E, Vandenberghe R, de Mendonca A, Butler CR, Gerhard A, Ducharme S, Ber ILE, Tiraboschi P, Santana I, Pasquier F, Levin J, Otto M, Sorbi S, Rohrer JD, Synofzik M; GENFI.

J Neurol Neurosurg Psychiatry. 2024


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 C9orf72GRN 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.