Increased neurofilament light chain blood levels in neurodegenerative neurological diseases.

Autor(es): 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

Resumo: 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.

Imprenta: PloS One, v. 8, n. 9, p. E75091, 2013

Identificador do objeto digital: 10.1371/journal.pone.0075091

Descritores: Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Public health

Data de publicação: 2013