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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; [...]

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

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  • Medientyp: E-Artikel
  • Titel: NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD: a large GENFI study
  • Beteiligte: 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; [...]
  • Erschienen: BMJ, 2024
  • Erschienen in: Journal of Neurology, Neurosurgery & Psychiatry
  • Sprache: Englisch
  • DOI: 10.1136/jnnp-2023-332464
  • ISSN: 0022-3050; 1468-330X
  • Schlagwörter: Psychiatry and Mental health ; Neurology (clinical) ; Surgery
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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<jats:italic>C9orf72</jats:italic>,<jats:italic>GRN</jats:italic>or<jats:italic>MAPT</jats:italic>; and n=139 within-family controls), each measured in three different international labs by Simoa HD-1 analyzer.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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.</jats:p></jats:sec>