Background: The quantification of neurofilament light chain (NfL) in blood and cerebrospinal fluid (CSF) has proved useful in many contexts, for the diagnosis and prognosis of various neurological disorders. There is, however, a diversity of practices between centers, essentially linked to the context of use (COU), analytical methods, consideration of comorbidities, determination of cut-points or use of interpretation scales. Finally, for the same biochemical profile, the interpretation and reporting of results may differ from one center to another, raising the question of test commutability. To date, no consensus has been reached between the different laboratories involved to define the most appropriate conclusions/comments based on COU and cut-points. This work is an essential step towards consensual harmonization of the clinical use of NfL after CSF and/or blood analysis in various neurological contexts, as advocated by the Alzheimer's Association "Biofluid Based Biomarkers PIA" working group.
Method: This international project involves 58 clinical laboratories in 16 countries, specializing in the biochemical diagnosis of neurological disorders. By means of a questionnaire, we obtained a description of the COU, pre-analytical and analytical (biological fluid and method used to quantify NfL) protocols of all the centers involved.
Results: Of the centers, 42% quantified NfL in CSF, 29% in serum and 28% in plasma, and 1% in dried blood spot. The COUs were as follows: Frontotemporal dementia (FTD, 17%), Alzheimer's disease (AD, 16%), multiple sclerosis (MS, 16%), amyotrophic lateral sclerosis (ALS, 11%), psychiatric syndrome (PS, 10%), Creutzfeldt-Jakob disease (CJD, 8%), Parkinson's disease (PD, 8%), peripheral neuropathy (PN, 7%) and traumatic brain injury (TBI, 7%). Most centers define pathological cut-points based on published literature and take age into account (50%).
Conclusion: Our initial results highlight the state of the art in terms of the clinical use of NfL analysis in CSF and blood in the context of different neurological diseases. We have now defined a coordinator for each COU subgroup and are organizing consensus meetings to harmonize the use and reporting of NfL measurements for the identified clinical applications. The results of these next steps will be presented.
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