Increased neurofilament light chain blood levels in neurodegenerative neurological diseases

• Published in: PloS one Vol. 8; no. 9; p. e75091
• Main Authors: Gaiottino, Johanna, Norgren, Niklas, Dobson, Ruth, Topping, Joanne, Nissim, Ahuva, Malaspina, Andrea, Bestwick, Jonathan P, Monsch, Andreas U, Regeniter, Axel, Lindberg, Raija L, Kappos, Ludwig, Leppert, David, Petzold, Axel, Giovannoni, Gavin, Kuhle, Jens
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.09.2013; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - blood; Amyotrophic Lateral Sclerosis - cerebrospinal fluid; Amyotrophic Lateral Sclerosis - diagnosis; Biomarkers; Biomarkers - blood; Blood; Blood levels; Brain research; Case-Control Studies; Central nervous system; Cerebrospinal fluid; Chains; Clinical trials; Correlation analysis; Cytoskeletal proteins; Cytoskeleton; Dentistry; Development and progression; Disease; Drugs; Electrochemical Techniques; Electrochemiluminescence; Female; Guillain-Barre syndrome; Guillain-Barre Syndrome - blood; Guillain-Barre Syndrome - cerebrospinal fluid; Guillain-Barre Syndrome - diagnosis; Hospitals; Humans; Immunoassay; Immunoglobulins; Laboratories; Light; Light levels; Longitudinal studies; Luminescent Measurements; Male; Medical research; Medicine; Middle Aged; Nervous system diseases; Neurodegeneration; Neurodegenerative diseases; Neurofilament Proteins - blood; Neurofilaments; Neurological complications; Neurological diseases; Neurology; Neuroprotection; Neurosciences; NMR; Nuclear magnetic resonance; Patients; Proteins; Serum levels; Substrates; Systematic review; United Kingdom > UK
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0075091

Neuronal damage is the morphological substrate of persisting neurological disability. Neurofilaments (Nf) are cytoskeletal proteins of neurons and their release into cerebrospinal fluid has shown encouraging results as a biomarker for neurodegeneration. This study aimed to validate the quantification of the Nf light chain (NfL) in blood samples, as a biofluid source easily accessible for longitudinal studies. We developed and applied a highly sensitive electrochemiluminescence (ECL) based immunoassay for quantification of NfL in blood and CSF. Patients with Alzheimer's disease (AD) (30.8 pg/ml, n=20), Guillain-Barré-syndrome (GBS) (79.4 pg/ml, n=19) or amyotrophic lateral sclerosis (ALS) (95.4 pg/ml, n=46) had higher serum NfL values than a control group of neurological patients without evidence of structural CNS damage (control patients, CP) (4.4 pg/ml, n=68, p<0.0001 for each comparison, p=0.002 for AD patients) and healthy controls (HC) (3.3 pg/ml, n=67, p<0.0001). Similar differences were seen in corresponding CSF samples. CSF and serum levels correlated in AD (r=0.48, p=0.033), GBS (r=0.79, p<0.0001) and ALS (r=0.70, p<0.0001), but not in CP (r=0.11, p=0.3739). The sensitivity and specificity of serum NfL for separating ALS from healthy controls was 91.3% and 91.0%. We developed and validated a novel ECL based sandwich immunoassay for the NfL protein in serum (NfL(Umea47:3)); levels in ALS were more than 20-fold higher than in controls. Our data supports further longitudinal studies of serum NfL in neurodegenerative diseases as a potential biomarker of on-going disease progression, and as a potential surrogate to quantify effects of neuroprotective drugs in clinical trials.