Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia

Lieke H. H. Meeter, Rebecca M. E. Steketee, Dina Salkovic, Maartje E. Vos, Murray Grossman, Corey T. McMillan, David J. Irwin, Adam L. Boxer, Julio C. Rojas, Nicholas T. Olney, Anna Karydas, Bruce L. Miller, Yolande A. L. Pijnenburg, Frederik Barkhof, Raquel Sánchez-Valle, Albert Lladó, Sergi Borrego-Ecija, Janine Diehl-Schmid, Timo Grimmer, Oliver GoldhardtAlexander F. Santillo, Oskar Hansson, Susanne Vestberg, Barbara Borroni, Alessandro Padovani, Daniela Galimberti, Elio Scarpini, Jonathan D. Rohrer, Ione O. C. Woollacott, Matthis Synofzik, Carlo Wilke, Alexandre de Mendonca, Rik Vandenberghe, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Wiro J. Niessen, Janne M. Papma, Harro Seelaar, Lize C. Jiskoot, Frank Jan de Jong, Laura Donker Kaat, Marta del Campo, Charlotte E. Teunissen, Esther E. Bron, Esther van den Berg, John C. van Swieten

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Background Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD. Methods This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset). Results CSF NfL levels were significantly higher in patients with SD (median: 2326 pg/mL, IQR: 1628-3593) than in controls (577 (446-766), p<0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test (r s =-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (r s =-0.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival. Conclusion CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities.

Original languageEnglish
Pages (from-to)997-1004
Number of pages8
JournalJournal of Neurology, Neurosurgery and Psychiatry
Issue number9
Publication statusPublished - 1 Sept 2019

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