Increased Neurofilament Light Chain Blood Levels in Neurodegenerative Neurological Diseases

被引:371
作者
Gaiottino, Johanna [1 ,2 ]
Norgren, Niklas [3 ]
Dobson, Ruth [1 ]
Topping, Joanne [1 ]
Nissim, Ahuva [2 ]
Malaspina, Andrea [1 ,4 ]
Bestwick, Jonathan P. [5 ]
Monsch, Andreas U. [6 ]
Regeniter, Axel [7 ]
Lindberg, Raija L. [8 ]
Kappos, Ludwig [8 ]
Leppert, David [8 ]
Petzold, Axel [9 ]
Giovannoni, Gavin [1 ]
Kuhle, Jens [1 ,2 ,8 ]
机构
[1] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst, London, England
[2] Queen Mary Univ London, John Vane Sci Ctr, Bone & Joint Res Unit, London, England
[3] UmanDiagnostics, Umea, Sweden
[4] North East London & Essex Reg MND Care Ctr, London, England
[5] Queen Mary Univ London, Barts & London Sch Med & Dent, Wolfson Inst Prevent Med, London, England
[6] Univ Basel Hosp, Dept Geriatr, Memory Clin, CH-4031 Basel, Switzerland
[7] Univ Basel Hosp, CH-4031 Basel, Switzerland
[8] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland
[9] UCL Inst Neurol, Dept Neuroinflammat, London, England
来源
PLOS ONE | 2013年 / 8卷 / 09期
关键词
AMYOTROPHIC-LATERAL-SCLEROSIS; CEREBROSPINAL-FLUID NEUROFILAMENT; AXONAL DAMAGE MARKERS; SUBUNIT PNF-H; HEAVY-CHAIN; NF-H; CSF; PROTEIN; BIOMARKERS; DIAGNOSIS;
D O I
10.1371/journal.pone.0075091
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-Barre-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.
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页数:9
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