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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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