Journal Article

Increased Neurofilament Light Chain Blood Levels in Neurodegenerative Neurological Diseases

Topping, Joanne, Nissim, Ahuva, Petzold, Axel, Dobson, Ruth, Kuhle, Jens, Gaiottino, Johanna, Monsch, Andreas U., Kappos, Ludwig, Bestwick, Jonathan P., Regeniter, Axel, Leppert, David, Giovannoni, Gavin, Norgren, Niklas, Malaspina, Andrea, Lindberg, Raija L.

2013

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 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 / Damage / 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