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Open Access 01-12-2013 | Research article

Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia

Authors: Maria Landqvist Waldö, Alexander Frizell Santillo, Ulla Passant, Henrik Zetterberg, Lars Rosengren, Christer Nilsson, Elisabet Englund

Published in: BMC Neurology | Issue 1/2013

Abstract

Background

Frontotemporal dementia (FTD) is recognised as a clinically and morphologically heterogeneous group of interrelated neurodegenerative conditions. One of the subtypes within this disease spectrum is the behavioural variant FTD (bvFTD). This is known to be a varied disorder with a mixture of tau-positive and tau-negative underlying pathologies. The other subtypes include semantic dementia (SD), which generally exhibits tau-negative pathology, and progressive non-fluent aphasia (PNFA), which is usually tau-positive. As the clinical presentation of these subtypes may overlap, a specific diagnosis can be difficult to attain and today no specific biomarker can predict the underlying pathology. Neurofilament light chain protein (NFL), a cytoskeletal constituent of intermediate filaments, is thought to reflect neuronal and axonal death when appearing in the cerebrospinal fluid (CSF). NFL has been shown to be elevated in CSF in patients with FTD compared with AD and controls. Our hypothesis was that the levels of NFL also differ between the subtypes of FTD and may indicate the underlying pathological subtype.

Methods

We retrospectively analysed data from previous CSF analyses in 34 FTD cases (23 bvFTD, seven SD, four PNFA), 20 AD cases, and 26 healthy controls. A separate group of 10 neuropathologically verified and subtyped FTD cases (seven tau-negative, three tau-positive) were also analysed.

Result

NFL levels were significantly higher in FTD compared with both AD (p<0.001) and controls (p<0.001). The NFL levels of SD and bvFTD were significantly higher (p<0.001) compared with AD. The biomarker profiles of PNFA and AD were similar. In the neuropathologically verified FTD cases, NFL was higher in the tau-negative than in the tau-positive cases (exact p=0.017).

Conclusions

The marked NFL elevation in some but not all FTD cases is likely to reflect the different underlying pathologies. The highest NFL values found in the SD group as well as in the neuropathologically verified tau-negative cases may be of subtype diagnostic value, if corroborated in larger patient cohorts. In bvFTD, a mixture of tau-positive and tau-negative underlying pathologies could possibly explain the intermediate NFL values.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2377/13/54/prepub

Title: Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia
Authors: Maria Landqvist Waldö
Alexander Frizell Santillo
Ulla Passant
Henrik Zetterberg
Lars Rosengren
Christer Nilsson
Elisabet Englund
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Neurology / Issue 1/2013
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/1471-2377-13-54

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Springer Medicine

Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia

Abstract

Background

Methods

Result

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Result

Conclusions

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