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

Title:	NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD: a large GENFI study
Authors:	Linnemann, Christoph; Wilke, Carlo; Mengel, David; Zetterberg, Henrik; Heller, Carolin; Kuhle, Jens; Bouzigues, Arabella; Russell, Lucy L; Foster, Phoebe H; Ferry-Bolder, Eve; Van Swieten, John Cornelis; Jiskoot, Lize C; Seelaar, Harro; Moreno, Fermin; Borroni, Barbara; Sánchez-Valle, Raquel; Galimberti, Daniela; Laforce, Robert; Graff, Caroline; Masellis, Mario; Tartaglia, Maria Carmela; Rowe, James Benedict; Finger, Elizabeth; Vandenberghe, Rik; de Mendonca, Alexandre; Butler, Chris R; Gerhard, Alexander; Ducharme, Simon; Ber, Isabelle L E; Tiraboschi, Pietro; Santana, Isabel; Pasquier, Florence; Levin, Johannes; Otto, Markus; Sorbi, Sandro; Rohrer, Jonathan Daniel; Synofzik; Matthis Annabel Nelson; Martina Bocchetta; David Cash; David L Thomas; Emily Todd; Hanya Benotmane; Jennifer Nicholas; Kiran Samra; Rachelle Shafei; Carolyn Timberlake; Thomas Cope; Timothy Rittman; Antonella Alberici; Enrico Premi; Roberto Gasparotti; Valentina Cantoni; Emanuele Buratti; Andrea Arighi; Chiara Fenoglio; Elio Scarpini; Giorgio Fumagalli; Vittoria Borracci; Giacomina Rossi; Giorgio Giaccone; Giuseppe Di Fede; Paola Caroppo; Pietro Tiraboschi; Sara Prioni; Veronica Redaelli; David Tang-Wai; Ekaterina Rogaeva; Miguel Castelo-Branco; Morris Freedman; Ron Keren; Sandra Black; Sara Mitchell; Christen Shoesmith; Robart Bartha; Rosa Rademakers; Jackie Poos; Janne M Papma; Lucia Giannini; Rick van Minkelen; Yolande Pijnenburg; Benedetta Nacmias; Camilla Ferrari; Cristina Polito; Gemma Lombardi; Valentina Bessi; Michele Veldsman; Christin Andersson; Hakan Thonberg; Linn Öijerstedt; Vesna Jelic; Paul Thompson; Tobias Langheinrich; Albert Lladó; Anna Antonell; Jaume Olives; Mircea Balasa; Nuria Bargalló; Sergi Borrego-Ecija; Ana Verdelho; Carolina Maruta; Catarina B Ferreira; Gabriel Miltenberger; Tiago Coelho; Frederico Simões do Couto; Alazne Gabilondo; Ana Gorostidi; Jorge Villanua; Marta Cañada; Mikel Tainta; Miren Zulaica; Myriam Barandiaran; Patricia Alves; Benjamin Bender; Lisa Graf; Annick Vogels; Mathieu Vandenbulcke; Van Damme Philip; Rose Bruffaerts; Koen Poesen; Pedro Rosa-Neto; Serge Gauthier; Agnès Camuzat; Alexis Brice; Anne Bertrand; Aurélie Funkiewiez; Daisy Rinaldi; Dario Saracino; Olivier Colliot; Sabrina Sayah; Catharina Prix; Elisabeth Wlasich; Olivia Wagemann; Sandra Loosli; Sonja Schönecker; Tobias Hoegen; Jolina Lombardi; Sarah Anderl-Straub; Adeline Rollin; Gregory Kuchcinski; Maxime Bertoux; Thibaud Lebouvier; Vincent Deramecourt; Beatriz Santiago; Diana Duro; Maria João Leitão; Maria Rosario Almeida; Miguel Tábuas-Pereira; Sónia Afonso
Contributors:	Christoph, Linnemann; Carlo, Wilke; David, Mengel; Henrik, Zetterberg; Carolin, Heller; Jens, Kuhle; Arabella, Bouzigue; 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, Maselli; 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; Synofzik; Annabel Nelson, Matthi; Bocchetta, Martina; Cash, David; L Thomas, David; Todd, Emily; Benotmane, Hanya; Nicholas, Jennifer; Samra, Kiran; Shafei, Rachelle; Timberlake, Carolyn; Cope, Thoma; Rittman, Timothy; Alberici, Antonella; Premi, Enrico; Gasparotti, Roberto; Cantoni, Valentina; Buratti, Emanuele; Arighi, Andrea; Fenoglio, Chiara; Scarpini, Elio; Fumagalli, Giorgio; Borracci, Vittoria; Rossi, Giacomina; Giaccone, Giorgio; Di Fede, Giuseppe; Caroppo, Paola; Tiraboschi, Pietro; Prioni, Sara; Redaelli, Veronica; Tang-Wai, David; Rogaeva, Ekaterina; Castelo-Branco, Miguel; Freedman, Morri; Keren, Ron; Black, Sandra; Mitchell, Sara; Shoesmith, Christen; Bartha, Robart; Rademakers, Rosa; Poos, Jackie; M Papma, Janne; Giannini, Lucia; van Minkelen, Rick; Pijnenburg, Yolande; Nacmias, Benedetta; Ferrari, Camilla; Polito, Cristina; Lombardi, Gemma; Bessi, Valentina; Veldsman, Michele; Andersson, Christin; Thonberg, Hakan; Öijerstedt, Linn; Jelic, Vesna; Thompson, Paul; Langheinrich, Tobia; Lladó, Albert; Antonell, Anna; Olives, Jaume; Balasa, Mircea; Bargalló, Nuria; Borrego-Ecija, Sergi; Verdelho, Ana
Publication Year:	2024
Collection:	Università degli Studi di Trento: CINECA IRIS
Subject Terms:	COGNITION; FRONTOTEMPORAL DEMENTIA; NEUROPSYCHIATRY
Description:	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.
Document Type:	article in journal/newspaper
Language:	English
Relation:	info:eu-repo/semantics/altIdentifier/pmid/38253362; info:eu-repo/semantics/altIdentifier/wos/WOS:001148397100001; volume:2024, 95; issue:9; firstpage:822; lastpage:828; numberofpages:7; journal:JOURNAL OF NEUROLOGY, NEUROSURGERY AND PSYCHIATRY; https://hdl.handle.net/11572/402070
DOI:	10.1136/jnnp-2023-332464
Availability:	https://hdl.handle.net/11572/402070; https://doi.org/10.1136/jnnp-2023-332464; https://jnnp.bmj.com/content/early/2024/01/31/jnnp-2023-332464.info
Rights:	info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by/4.0/
Accession Number:	edsbas.6FF62845
Database:	BASE