title: Multicentre quality control evaluation of different biomarker candidates for amyotrophic lateral sclerosis.
abstract: 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.
authors.affiliation: Department of Neurology, University of Ulm , Ulm , Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lehnert
authors.forename: Julia
authors.initials: J
authors.lastname: Costa
authors.forename: Mamede
authors.initials: M
authors.lastname: de Carvalho
authors.forename: Janine
authors.initials: J
authors.lastname: Kirby
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kuzma-Kozakiewicz
authors.forename: Claudia
authors.initials: C
authors.lastname: Morelli
authors.forename: Wim
authors.initials: W
authors.lastname: Robberecht
authors.forename: Pamela
authors.initials: P
authors.lastname: Shaw
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Silani
authors.forename: Petra
authors.initials: P
authors.lastname: Steinacker
authors.forename: Hayrettin
authors.initials: H
authors.lastname: Tumani
authors.forename: Philip
authors.initials: P
authors.lastname: Van Damme
authors.forename: Albert
authors.initials: A
authors.lastname: Ludolph
authors.forename: Markus
authors.initials: M
authors.lastname: Otto
mesh_terms: D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D018932:Chemokine CCL2 / Q000134:cerebrospinal fluid; D055316:Cystatin C / Q000134:cerebrospinal fluid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D064568:S100 Calcium Binding Protein beta Subunit / Q000134:cerebrospinal fluid; D018709:Statistics, Nonparametric; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C111835:CCL2 protein, human; C525030:CST3 protein, human; D018932:Chemokine CCL2; D055316:Cystatin C; D016900:Neurofilament Proteins; D010446:Peptide Fragments; D064568:S100 Calcium Binding Protein beta Subunit; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; C051774:neurofilament protein H
keywords: ALS; CSF biomarker; MCP-1; amyloid-beta; cystatin C; multicentre sample-collection approach with centralized sample processing; tau