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Increased Neurofilament Light Chain Blood Levels in Neurodegenerative Neurological Diseases
Open accessAbstract
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.
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Metadata
- Authors
- Gaiottino, J., Norgren, N., Dobson, R., Topping, J., Nissim, A., Malaspina, A., Bestwick, J. P., Monsch, A. U., Regeniter, A., Lindberg, R. L., Kappos, L., Leppert, D., Petzold, A., Giovannoni, G., & Kuhle, J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-09-20
- Volume
- 8
- Issue
- 9
- Pages
- e75091
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2157203036
- Cited by
- 486
- References
- 2
- FWCI
- 11.97
- Type
- journal article
- Language
- en
- Open access
- gold
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