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Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia
Authors
Frederik Barkhof
Luisa Benussi
+45 more
Giuliano Binetti
Sergi Borrego-Ecija
Barbara Borroni
Adam L. Boxer
Esther E. Bron
Frank Jan de Jong
Alexandre De Mendonça
Marta Del Campo
Janine Diehl-Schmid
Laura Donker Kaat
Daniela Galimberti
Roberta Ghidoni
Oliver Goldhardt
Timo Grimmer
Murray Grossman
Oskar Hansson
David J. Irwin
Lize C. Jiskoot
Anna Karydas
Albert Lladó
Corey T. McMillan
Lieke H. H. Meeter
Bruce L. Miller
Wiro J. Niessen
Nicholas T. Olney
Alessandro Padovani
Janne M. Papma
Yolande A. L. Pijnenburg
Jonathan D. Rohrer
Julio C. Rojas
Dina Salkovic
Alexander F. Santillo
Elio Scarpini
Harro Seelaar
Rebecca M. E. Steketee
Matthis Synofzik
Raquel Sánchez-Valle
Charlotte E. Teunissen
Esther Van den Berg
John C. Van Swieten
Rik Vandenberghe
Susanne Vestberg
Maartje E. Vos
Carlo Wilke
Ione O. C. Woollacott
Publication date
1 January 2019
Publisher
'BMJ'
Doi
Cite
Abstract
© Author(s) (or their employer(s)) 2019. 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/.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 (rs =-0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (rs =-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.This study was funded by a Memorabel grant from Deltaplan Dementie (The Netherlands Organisation for Health Research and Development, and Alzheimer Nederland grant number 7330598105), National Institutes of Health (Grants AG010124, AG032953, AG043503, NS088341, AG017586, AG052943, AG038490), the Wyncote Foundation, Dana Foundation, Brightfocus Foundation, Penn Institute on Aging, Pla estratègic de recerca i innovació en salut 2016-2020, Catalan Department of Health (grant number SLT002/16/00408), Italian Ministry of Health (Ricerca Corrente) and the German Federal Ministry of Education and Research (FTLDc 01GI1007A). MS was supported by the Else Kröner-Fresenius-Stiftung. CW was supported by the Vaillant Stiftunginfo:eu-repo/semantics/publishedVersio
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