Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that mainly causes degeneration of the upper and lower motor neurons, ultimately leading to paralysis and death within three to five years after first symptoms. The pathological mechanisms leading to ALS are still not completely understood. Several biomarker candidates have been proposed in cerebrospinal fluid (CSF). However, none of these has successfully translated into clinical routine. Part of the reason for this failure to translate may relate to differences across laboratories. For this reason, several of the most commonly used ALS biomarker candidates were evaluated on clinically well-defined ALS samples from six European centres in a multicentre sample-collection approach with centralized sample processing. Results showed that phosphorylated neurofilament heavy chain differentiated between ALS and control cases in all centres. We therefore propose that measurement of phosphorylated neurofilaments in CSF is the most promising candidate for translation into the clinical setting and might serve as a benchmark for other biomarker candidates.
Acknowledgements
This project was supported by the European Commission (JNPD Sophia, JNPD Biomark-APD, NADINE), the Thierry Latran Foundation, the BMBF (FTLD consortium) and the Stiftung Baden-Württemberg. This is an EU Joint Programme - Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organisations under the aegis of JPND - www.jpnd.eu: France, Agence Nationale de la Recherche; Germany, Bundesministerium für Bildung und Forschung; Ireland, Health Research Board; Italy, Ministero della Salute; The Netherlands, The Netherlands Organisation for Health Research and Development; Poland, Narodowe Centrum Badań i Rozwoju; Portugal, Fundação a Ciência e a Tecnologia; Spain, Ministerio de Ciencia e Innovación; Switzerland, Schweizerischer Nationalfonds zur Förderung der wissenschaftlichen Forschung; Turkey, Tübitak; United Kingdom, Medical Research Council.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.