Cerebrospinal fluid neurofilament light concentration in motor neuron disease and frontotemporal dementia predicts survival

Abstract

Objective: 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 Sahlgrenska University Hospital to produce a dataset of CSF NFL concentrations and mortality information for 715 MND patients, 87 FTD patients, and 107 healthy controls. Biomarker concentrations were analysed in relation to recorded cause of death and time of death.

Results: MND patients had significantly higher CSF NFL concentrations than FTD patients. Both groups had significantly higher concentrations than the healthy controls (mean 709% increase in MND and 307% increase in FTD). Higher concentrations of CSF NFL were associated with shorter survival in both MND and FTD.

Conclusions: The results of this study strengthen the notion of CSF NFL as a useful tool for determining disease intensity in MND and FTD patients. Further studies in patient cohorts with clinically subtyped and genetically classified diagnoses are needed.

Keywords:

• Biomarkers in CSF
• neurofilament light protein
• motor neuron disease
• amyotrophic lateral sclerosis
• frontotemporal dementia

Acknowledgements

We would thank Fakhri Quraishi and Lars Holm for technical assistance. This study was supported by grants from the Swedish Research Council, European Research Council, the Knut and Alice Wallenberg Foundation, the Torsten Söderberg Foundation, Sahlgrenska University Hospital and the Sahlgrenska Academy.

Declaration of interest

None of the authors of this manuscript report any disclosures. The authors report no conflicts of interest.

We would thank Fakhri Quraishi and Lars Holm for technical assistance. This study was supported by grants from the Swedish Research Council, European Research Council, the Knut and Alice Wallenberg Foundation, the Torsten Söderberg Foundation, Sahlgrenska University Hospital and the Sahlgrenska Academy.