. Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis. Neurology. 2015 Jun 2;84(22):2247-57. Epub 2015 May 1 PubMed.


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  1. The finding that neurofilament light chain (NFL) in the CSF is an independent prognostic marker for ALS is very interesting. This study is important because the authors have used longitudinal data and shown that there is little change over the course of the disease. Although the numbers are small and the study sample atypical, it is difficult to avoid these biases in longitudinal studies involving CSF sampling, and the authors acknowledge that. CSF NFL has more potential as a prognostic than diagnostic marker, unless it can be shown that at an early stage of disease NFL levels can correctly classify ALS mimics as not being ALS.

    View all comments by Ammar Al-Chalabi
  2. This paper by Lu et al. has the potential to become a landmark paper in ALS research. Although they have focused on using neurofilament light chain (NfL) in blood as a prognostic marker, they could show — using for the first time a relevant number of prospectively investigated patients — that ALS patients have clearly higher NfL levels in blood compared with controls. Indeed, higher a level of NfL seems to be associated with a worse prognosis, even if it is a bit counterintuitive that NfL does not seem to rise in the follow-up investigations. This certainly has to be further investigated, especially if NfL might be used as inclusion or exclusion criteria for treatment trials.

    In my view, their paper opens up for discussion whether neurofilaments should be included in diagnostic work-up. As there is still an overlap between patients and healthy controls, cerebrospinal fluid might be the better choice for such a differential diagnostic. However, further prospective studies with differential diagnostic-relevant cases must be investigated. Their work also raises the question of whether follow-up measurements in blood might give an objective marker of disease onset in patients at risk.

    Five years ago during a Reisenburg conference a clear roadmap for biomarkers on ALS was formulated. The groups in Oxford and London made a major step forward on this agenda.

    View all comments by Markus Otto

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