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Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/28315
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dc.contributor.authorLinnemann, C-
dc.contributor.authorWilke, C-
dc.contributor.authorMengel, D-
dc.contributor.authorZetterberg, H-
dc.contributor.authorHeller, C-
dc.contributor.authorKuhle, J-
dc.contributor.authorBouzigues, A-
dc.contributor.authorRussell, LL-
dc.contributor.authorFoster, PH-
dc.contributor.authorFerry-Bolder, E-
dc.contributor.authorVan Swieten, JC-
dc.contributor.authorJiskoot, LC-
dc.contributor.authorSeelaar, H-
dc.contributor.authorMoreno, F-
dc.contributor.authorBorroni, B-
dc.contributor.authorSánchez-Valle, R-
dc.contributor.authorGalimberti, D-
dc.contributor.authorLaforce, R-
dc.contributor.authorGraff, C-
dc.contributor.authorMasellis, M-
dc.contributor.authorTartaglia, MC-
dc.contributor.authorRowe, JB-
dc.contributor.authorFinger, E-
dc.contributor.authorVandenberghe, R-
dc.contributor.authorde Mendonca, A-
dc.contributor.authorButler, CR-
dc.contributor.authorGerhard, A-
dc.contributor.authorDucharme, S-
dc.contributor.authorBer, ILE-
dc.contributor.authorTiraboschi, P-
dc.contributor.authorSantana, I-
dc.contributor.authorPasquier, F-
dc.contributor.authorLevin, J-
dc.contributor.authorOtto, M-
dc.contributor.authorSorbi, S-
dc.contributor.authorRohrer, JD-
dc.contributor.authorSynofzik, M-
dc.date.accessioned2024-02-14T17:15:51Z-
dc.date.available2024-02-14T17:15:51Z-
dc.date.issued2024-01-19-
dc.identifierORCiD: Christoph Linnemann https://orcid.org/0000-0001-5901-2629-
dc.identifierORCiD: Henrik Zetterberg https://orcid.org/0000-0003-3930-4354-
dc.identifierORCiD: Carolin Heller https://orcid.org/0000-0002-1934-6162-
dc.identifierORCiD: John Cornelis Van Swieten https://orcid.org/0000-0001-6278-6844-
dc.identifierORCiD: Lize C Jiskoot https://orcid.org/0000-0002-1120-1858-
dc.identifierORCiD: Harro Seelaar https://orcid.org/0000-0003-1989-7527-
dc.identifierORCID iD: Daniela Galimberti https://orcid.org/0000-0002-9284-5953-
dc.identifierORCiD: James Benedict Rowe https://orcid.org/0000-0001-7216-8679-
dc.identifierORCiD: Elizabeth Finger https://orcid.org/0000-0003-4461-7427-
dc.identifierORCiD: Alexander Gerhard https://orcid.org/0000-0002-8071-6062-
dc.identifierORCiD: Simon Ducharme https://orcid.org/0000-0002-7309-1113-
dc.identifierORCiD: Isabelle L E Ber https://orcid.org/0000-0002-2508-5181-
dc.identifierORCiD: Pietro Tirabosch https://orcid.org/0000-0002-2171-1720-
dc.identifierORCiD: Sandro Sorbi https://orcid.org/0000-0002-0380-6670-
dc.identifierORCiD: Jonathan Daniel Rohrer https://orcid.org/0000-0002-6155-8417-
dc.identifierORCiD: Matthis Synofzik https://orcid.org/0000-0002-2280-7273-
dc.identifierORCiD: Martina Bocchetta https://orcid.org/0000-0003-1814-5024-
dc.identifier.citationLinnemann C. et al. on behalf of GENFI (2024) 'NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD: a large GENFI study', Journal of Neurology, Neurosurgery & Psychiatry, 0 (ahead of print), pp. 1 - xx.. doi: 10.1136/jnnp-2023-332464.en_US
dc.identifier.issn0022-3050-
dc.identifier.urihttps://bura.brunel.ac.uk/handle/2438/28315-
dc.descriptionSupplementary Data: This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content. Data supplement 1 is available online at: https://jnnp.bmj.com/highwire/filestream/221824/field_highwire_adjunct_files/0/jnnp-2023-332464supp001_data_supplement.pdf .en_US
dc.description.abstractBackground: 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.en_US
dc.description.sponsorshipJCVS was supported by the Dioraphte Foundation grant 09-02-03-00, Association for Frontotemporal Dementias Research Grant 2009, Netherlands Organization for Scientific Research grant HCMI 056-13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733051042), Alzheimer Nederland and the Bluefield Project. FM received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease. RS-V is supported by Alzheimer’s Research UK Clinical Research Training Fellowship (ARUK-CRF2017B-2) and has received funding from Fundació Marató de TV3, Spain (grant no. 20143810). DG received support from the EU Joint Programme—Neurodegenerative Disease Research and the Italian Ministry of Health (PreFrontALS) grant 733051042. CG received funding from EU Joint Programme—Neurodegenerative Disease Research-refrontals VR Dnr 529-2014-7504, VR 2015-02926 and 2018-02754, the Swedish FTD Inititative-Schörling Foundation, Alzheimer Foundation, Brain Foundation and Stockholm County Council ALF. MM has received funding from a Canadian Institute of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. JBR has received funding from the Wellcome Trust (103838) and is supported by the Cambridge University Centre for Frontotemporal Dementia, the Medical Research Council (SUAG/051 G101400) and the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215-20014). EF has received funding from a Canadian Institute of Health Research grant #327387. RV has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. JL received funding for this work by the Deutsche Forschungsgemeinschaft German Research Foundation under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy—ID 390857198). MO has received funding from Germany’s Federal Ministry of Education and Research (BMBF). JDR is supported by the Bluefield Project and the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and a Miriam Marks Brain Research UK Senior Fellowship. Several authors of this publication (JCVS, MS, RV, AdM, MO, RV and JDR) are members of the European Reference Network for Rare Neurological Diseases (ERN-RND)—Project ID No 739510. This work was also supported by the EU Joint Programme—Neurodegenerative Disease Research GENFI-PROX grant (2019-02248; to JDR, MO, BB, CG, JCVS and MS, and by the Clinician Scientist programme 'PRECISE.net' funded by the Else Kröner-Fresenius-Stiftung (to CW, DM and MS). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2022-01018 and #2019-02397), the European Union’s Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C, and #ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), the European Union Joint Programme—Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre and the UK Dementia Research Institute at UCL (UKDRI-1003).en_US
dc.format.extent1 - 11-
dc.format.mediumPrint-Electronic-
dc.languageEnglish-
dc.language.isoen_USen_US
dc.publisherBMJen_US
dc.rightsCopyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.-
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.titleNfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD: a large GENFI studyen_US
dc.typeArticleen_US
dc.identifier.doihttps://doi.org/10.1136/jnnp-2023-332464-
dc.relation.isPartOfJournal of Neurology, Neurosurgery & Psychiatry-
pubs.publication-statusPublished online-
pubs.volume0-
dc.identifier.eissn1468-330X-
dc.rights.holderAuthor(s) (or their employer(s))-
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