Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia.

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 (

CONCLUSION

CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities.

Informations de copyright

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: The authors report no conflicts of interest relevant to this study. LHHM is supported by Alzheimer Nederland (grant number WE.09 2014 04). ALB and JCR are supported by the NIH (U54NS092089, R01AG031278, R01AG038791, R01AG032306, R01AG022983) and the Association for Frontotemporal Degeneration. ALB, JCR and LDK are supported by the Bluefield Project to Cure Frontotemporal Dementia. The Dementia Research Centre is supported by Alzheimer’s Research UK, Brain Research Trust and The Wolfson Foundation. This work was supported by the NIHR Queen Square Dementia Biomedical Research Unit, the NIHR UCL/H Biomedical Research Centre and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility as well as an Alzheimer’s Society grant (AS-PG-16-007). JDR is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). IOCW is supported by an MRC Clinical Research Training Fellowship (MR/M018288/1). AS is supported by the Swedish Society for Medical Research. CET is supported by ZonMW Memorabel Program (grant number 733050206). JCvS is supported by the Dioraphte Foundation.