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Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia

Published on May 23, 2019in Journal of Neurology, Neurosurgery, and Psychiatry 8.27
· DOI :10.1136/jnnp-2018-319784
Lieke H.H. Meeter7
Estimated H-index: 7
(EUR: Erasmus University Rotterdam),
Rebecca M. E. Steketee6
Estimated H-index: 6
(EUR: Erasmus University Rotterdam)
+ 44 AuthorsJohn VanSwieten68
Estimated H-index: 68
(EUR: Erasmus University Rotterdam)
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Abstract
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.
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References36
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Published on Dec 1, 2018in Alzheimer's Research & Therapy
Joery Goossens5
Estimated H-index: 5
(University of Antwerp),
Maria Bjerke7
Estimated H-index: 7
(University of Antwerp)
+ 10 AuthorsPeter Paul De Deyn82
Estimated H-index: 82
(University of Antwerp)
Background We explored the diagnostic performance of cerebrospinal fluid (CSF) biomarkers in allowing differentiation between frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD), as well as between FTLD pathological subtypes.
Published on Apr 3, 2018in Neurology 8.69
Lieke H.H. Meeter7
Estimated H-index: 7
,
Everard G.B. Vijverberg4
Estimated H-index: 4
+ 7 AuthorsYolande A.L. Pijnenburg45
Estimated H-index: 45
Objective To examine the clinical value of neurofilament light chain (NfL) and the phospho-tau/total tau ratio (p/t-tau) across the entire frontotemporal dementia (FTD) spectrum in a large, well-defined cohort. Methods CSF NfL and p/t-tau levels were studied in 361 patients with FTD: 179 behavioral variant FTD, 17 FTD with motor neuron disease (FTD-MND), 36 semantic variant primary progressive aphasia (PPA), 19 nonfluent variant PPA, 4 logopenic variant PPA (lvPPA), 42 corticobasal syndrome, and...
Published on Oct 1, 2017in Neurobiology of Aging 4.40
Joana B. Pereira18
Estimated H-index: 18
(KI: Karolinska Institutet),
Eric Westman37
Estimated H-index: 37
(KI: Karolinska Institutet)
+ 1 AuthorsAlzheimer's Disease Neuroimaging Initiative12
Estimated H-index: 12
The aggregation and deposition of amyloid-β (Aβ) peptides into plaques is an early event in Alzheimer's disease (AD), which is followed by different aspects of neurodegeneration that can be measured in the cerebrospinal fluid (CSF) or plasma using neurofilament light (NFL), neurogranin (Ng), total Tau (T-Tau), and phosphorylated tau (P-Tau) levels. The relationship between these biomarkers and regional brain atrophy across the different stages of AD remains largely unexplored. In this study, we ...
Published on Jul 3, 2017in Amyotrophic Lateral Sclerosis 2.88
Tobias Skillbäck12
Estimated H-index: 12
(Sahlgrenska University Hospital),
Niklas Mattsson42
Estimated H-index: 42
(Lund University)
+ 1 AuthorsHenrik Zetterberg84
Estimated H-index: 84
(UCL Institute of Neurology)
AbstractObjective: To aid diagnostics, patient stratification and studies seeking to find treatments for the related diseases motor neuron disease (MND) and frontotemporal dementia (FTD), there is a need to establish a way to assess disease severity and the amount of ongoing neurodegeneration. Previous studies have suggested that cerebrospinal fluid (CSF) neurofilament light (NFL) may serve this purpose.Methods: We cross-referenced the Swedish mortality registry with the laboratory database at S...
Published on Jun 16, 2017in Nature Reviews Neurology 21.16
Lieke H.H. Meeter7
Estimated H-index: 7
,
Laura Donker Kaat9
Estimated H-index: 9
+ 1 AuthorsJohn VanSwieten68
Estimated H-index: 68
Reliable biomarkers for frontotemporal dementia (FTD) are required for accurate discrimination between dementia types, prediction of clinical progression and tailoring of pharmacological interventions. This Review discusses the increasing number of available biomarkers for FTD — including novel imaging modalities and fluid biomarkers — and the future challenges in their implementation.
Published on Mar 7, 2017in Neurology 8.69
Petra Steinacker27
Estimated H-index: 27
,
Elisa Semler3
Estimated H-index: 3
+ 20 AuthorsJan Kassubek51
Estimated H-index: 51
Objective: To assess the utility of serum neurofilament for diagnosis and monitoring of primary progressive aphasia (PPA) variants. Methods: We investigated neurofilament light chain (NF-L) levels in blood of 99 patients with PPA (40 with nonfluent variant PPA [nfvPPA], 38 with semantic variant PPA [svPPA], 21 with logopenic variant PPA [lvPPA]) and compared diagnostic performance with that reached by CSF NF-L, phosphorylated neurofilament heavy chain (pNF-H), β-amyloid (Aβ 1-42 ), tau, and phos...
Published on Dec 1, 2016in Alzheimer's Research & Therapy
Ramon Landin-Romero14
Estimated H-index: 14
(UNSW: University of New South Wales),
Rachel Tan13
Estimated H-index: 13
(UNSW: University of New South Wales)
+ 1 AuthorsFiona Kumfor13
Estimated H-index: 13
(UNSW: University of New South Wales)
Progressive and relatively circumscribed loss of semantic knowledge, referred to as semantic dementia (SD) which falls under the broader umbrella of frontotemporal dementia, was officially identified as a clinical syndrome less than 50 years ago. Here, we review recent neuroimaging, pathological, and genetic research in SD. From a neuroimaging perspective, SD is characterised by hallmark asymmetrical atrophy of the anterior temporal pole and anterior fusiform gyrus, which is usually left lateral...
Published on Nov 1, 2016in Journal of Neurology, Neurosurgery, and Psychiatry 8.27
Carlo Wilke9
Estimated H-index: 9
(University of Tübingen),
Oliver Preische5
Estimated H-index: 5
(University of Tübingen)
+ 7 AuthorsMatthis Synofzik35
Estimated H-index: 35
(University of Tübingen)
Frontotemporal dementia (FTD) is a devastating neurodegenerative disorder for which readily available biomarkers are needed to monitor disease progression and response to future therapies. Neurofilament light chain (NfL), a cytoskeletal protein, is elevated in the cerebrospinal fluid (CSF) of patients with FTD, correlating with disease severity.1 ,2 As CSF sampling is more invasive than venepuncture and requires higher subject compliance, we tested the hypothesis that NfL levels in FTD are eleva...
Published on Sep 27, 2016in Neurology 8.69
Jonathan D. Rohrer48
Estimated H-index: 48
,
Ione O.C. Woollacott9
Estimated H-index: 9
+ 16 AuthorsSebastien Ourselin55
Estimated H-index: 55
Objective: To investigate serum neurofilament light chain (NfL) concentrations in frontotemporal dementia (FTD) and to see whether they are associated with the severity of disease. Methods: Serum samples were collected from 74 participants (34 with behavioral variant FTD [bvFTD], 3 with FTD and motor neuron disease and 37 with primary progressive aphasia [PPA]) and 28 healthy controls. Twenty-four of the FTD participants carried a pathogenic mutation in C9orf72 (9), microtubule-associated protei...
Published on Aug 1, 2016in Journal of Neurochemistry 4.87
Elizabeth Gordon8
Estimated H-index: 8
(UCL Institute of Neurology),
Jonathan D. Rohrer48
Estimated H-index: 48
(UCL Institute of Neurology),
Nick C. Fox112
Estimated H-index: 112
(UCL Institute of Neurology)
Frontotemporal dementia (FTD) is a clinically and neuroanatomically heterogeneous neurodegenerative disorder with multiple underlying genetic and pathological causes. Whilst initial neuroimaging studies highlighted the presence of frontal and temporal lobe atrophy or hypometabolism as the unifying feature in patients with FTD, more detailed studies have revealed diverse patterns across individuals, with variable frontal or temporal predominance, differing degrees of asymmetry, and the involvemen...
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