Increased neurofilament light chain blood levels in neurodegenerative neurological diseases.
OBJECTIVE
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.


METHODS
We developed and applied a highly sensitive electrochemiluminescence (ECL) based immunoassay for quantification of NfL in blood and CSF.


RESULTS
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%.


CONCLUSIONS
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.
Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom ; Bone & Joint Research Unit, John Vane Science Centre, Queen Mary University of London, London, United Kingdom.
Johanna
J
Gaiottino
Niklas
N
Norgren
Ruth
R
Dobson
Joanne
J
Topping
Ahuva
A
Nissim
Andrea
A
Malaspina
Jonathan P
JP
Bestwick
Andreas U
AU
Monsch
Axel
A
Regeniter
Raija L
RL
Lindberg
Ludwig
L
Kappos
David
D
Leppert
Axel
A
Petzold
Gavin
G
Giovannoni
Jens
J
Kuhle
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D055664:Electrochemical Techniques; D005260:Female; D020275:Guillain-Barre Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D006801:Humans; D007118:Immunoassay; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000097:blood*
D015415:Biomarkers; D016900:Neurofilament Proteins; C044882:neurofilament protein L