Multicentre quality control evaluation of different biomarker candidates for amyotrophic lateral sclerosis

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.