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Open Access Research article

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

Maria Landqvist Waldö1*, Alexander Frizell Santillo1, Ulla Passant1, Henrik Zetterberg34, Lars Rosengren5, Christer Nilsson1 and Elisabet Englund2

Author Affiliations

1 Section of Geriatric Psychiatry, Department of Clinical Sciences, Lund University Hospital, Klinikgatan 22, Lund SE-221 85, Sweden

2 Section of Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden

3 Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden

4 UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom

5 Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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BMC Neurology 2013, 13:54  doi:10.1186/1471-2377-13-54

Published: 29 May 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.

Keywords:
Semantic dementia; Neuropathology; Clinical diagnosis