Increased neurofilament light chain blood levels in neurodegenerative neurological diseases.
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 quantificatio...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3779219?pdf=render |
| _version_ | 1811306033143873536 |
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| author | Johanna Gaiottino Niklas Norgren Ruth Dobson Joanne Topping Ahuva Nissim Andrea Malaspina Jonathan P Bestwick Andreas U Monsch Axel Regeniter Raija L Lindberg Ludwig Kappos David Leppert Axel Petzold Gavin Giovannoni Jens Kuhle |
| author_facet | Johanna Gaiottino Niklas Norgren Ruth Dobson Joanne Topping Ahuva Nissim Andrea Malaspina Jonathan P Bestwick Andreas U Monsch Axel Regeniter Raija L Lindberg Ludwig Kappos David Leppert Axel Petzold Gavin Giovannoni Jens Kuhle |
| author_sort | Johanna Gaiottino |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T08:37:05Z |
| format | Article |
| id | doaj.art-d03fb4a051234c338a5db3bae6034e5f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T08:37:05Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d03fb4a051234c338a5db3bae6034e5f2022-12-22T02:54:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7509110.1371/journal.pone.0075091Increased neurofilament light chain blood levels in neurodegenerative neurological diseases.Johanna GaiottinoNiklas NorgrenRuth DobsonJoanne ToppingAhuva NissimAndrea MalaspinaJonathan P BestwickAndreas U MonschAxel RegeniterRaija L LindbergLudwig KapposDavid LeppertAxel PetzoldGavin GiovannoniJens KuhleNeuronal 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.http://europepmc.org/articles/PMC3779219?pdf=render |
| spellingShingle | Johanna Gaiottino Niklas Norgren Ruth Dobson Joanne Topping Ahuva Nissim Andrea Malaspina Jonathan P Bestwick Andreas U Monsch Axel Regeniter Raija L Lindberg Ludwig Kappos David Leppert Axel Petzold Gavin Giovannoni Jens Kuhle Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. PLoS ONE |
| title | Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. |
| title_full | Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. |
| title_fullStr | Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. |
| title_full_unstemmed | Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. |
| title_short | Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. |
| title_sort | increased neurofilament light chain blood levels in neurodegenerative neurological diseases |
| url | http://europepmc.org/articles/PMC3779219?pdf=render |
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