Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology.
Axonal damage leads to the release of neurofilament light chain (NFL), which enters the CSF or blood. In this work, an assay kit for plasma NFL utilizing immunomagnetic reduction (IMR) was developed. Antibodies against NFL were immobilized on magnetic nanoparticles to develop an IMR NFL kit. The pre...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0234519 |
| _version_ | 1819018554973880320 |
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| author | Huei-Chun Liu Wei-Che Lin Ming-Jang Chiu Cheng-Hsien Lu Chin-Yi Lin Shieh-Yueh Yang |
| author_facet | Huei-Chun Liu Wei-Che Lin Ming-Jang Chiu Cheng-Hsien Lu Chin-Yi Lin Shieh-Yueh Yang |
| author_sort | Huei-Chun Liu |
| collection | DOAJ |
| description | Axonal damage leads to the release of neurofilament light chain (NFL), which enters the CSF or blood. In this work, an assay kit for plasma NFL utilizing immunomagnetic reduction (IMR) was developed. Antibodies against NFL were immobilized on magnetic nanoparticles to develop an IMR NFL kit. The preclinical properties, such as the standard curve, limit of detection (LoD), and dynamic range, were characterized. Thirty-one normal controls (NC), fifty-two patients with Parkinson's disease (PD) or PD dementia (PDD) and thirty-one patients with Alzheimer's disease (AD) were enrolled in the study evaluating the plasma NFL assay using an IMR kit. T-tests and receiver operating characteristic (ROC) curve analysis were performed to investigate the capability for discrimination among the clinical groups according to plasma NFL levels. The LoD of the NFL assay using the IMR kit was found to be 0.18 fg/ml. The dynamic range of the NFL assay reached 1000 pg/ml. The NC group showed a plasma NFL level of 7.70 ± 4.00 pg/ml, which is significantly lower than that of the PD/PDD (15.85 ± 7.82 pg/ml, p < 0.001) and AD (19.24 ± 8.99 pg/ml, p < 0.001) groups. A significant difference in plasma NFL levels was determined between the PD and AD groups (p < 0.01). Through ROC curve analysis, the cut-off value of the plasma NFL concentration for differentiating NCs from dementia patients (AD and PD/PDD) was found to be 12.71 pg/ml, with a clinical sensitivity and specificity of 73.5% and 90.3%, respectively. The AUC was 0.868. Furthermore, the cut-off value of the plasma NFL concentration for discriminating AD from PD/PDD was found to be 18.02 pg/ml, with a clinical sensitivity and specificity of 61.3% and 65.4%, respectively. The AUC was 0.630. An ultrasensitive assay for measuring plasma NFL utilizing IMR technology was developed. Clear differences in plasma NFL concentrations were observed among NCs and PD and AD patients. These results imply that the determination of plasma NFL is promising not only for screening dementia but also for differential diagnosis. |
| first_indexed | 2024-12-21T03:21:16Z |
| format | Article |
| id | doaj.art-c60cd36fcef4464d89c459ae27bb62c1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T03:21:16Z |
| publishDate | 2020-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-c60cd36fcef4464d89c459ae27bb62c12022-12-21T19:17:41ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01156e023451910.1371/journal.pone.0234519Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology.Huei-Chun LiuWei-Che LinMing-Jang ChiuCheng-Hsien LuChin-Yi LinShieh-Yueh YangAxonal damage leads to the release of neurofilament light chain (NFL), which enters the CSF or blood. In this work, an assay kit for plasma NFL utilizing immunomagnetic reduction (IMR) was developed. Antibodies against NFL were immobilized on magnetic nanoparticles to develop an IMR NFL kit. The preclinical properties, such as the standard curve, limit of detection (LoD), and dynamic range, were characterized. Thirty-one normal controls (NC), fifty-two patients with Parkinson's disease (PD) or PD dementia (PDD) and thirty-one patients with Alzheimer's disease (AD) were enrolled in the study evaluating the plasma NFL assay using an IMR kit. T-tests and receiver operating characteristic (ROC) curve analysis were performed to investigate the capability for discrimination among the clinical groups according to plasma NFL levels. The LoD of the NFL assay using the IMR kit was found to be 0.18 fg/ml. The dynamic range of the NFL assay reached 1000 pg/ml. The NC group showed a plasma NFL level of 7.70 ± 4.00 pg/ml, which is significantly lower than that of the PD/PDD (15.85 ± 7.82 pg/ml, p < 0.001) and AD (19.24 ± 8.99 pg/ml, p < 0.001) groups. A significant difference in plasma NFL levels was determined between the PD and AD groups (p < 0.01). Through ROC curve analysis, the cut-off value of the plasma NFL concentration for differentiating NCs from dementia patients (AD and PD/PDD) was found to be 12.71 pg/ml, with a clinical sensitivity and specificity of 73.5% and 90.3%, respectively. The AUC was 0.868. Furthermore, the cut-off value of the plasma NFL concentration for discriminating AD from PD/PDD was found to be 18.02 pg/ml, with a clinical sensitivity and specificity of 61.3% and 65.4%, respectively. The AUC was 0.630. An ultrasensitive assay for measuring plasma NFL utilizing IMR technology was developed. Clear differences in plasma NFL concentrations were observed among NCs and PD and AD patients. These results imply that the determination of plasma NFL is promising not only for screening dementia but also for differential diagnosis.https://doi.org/10.1371/journal.pone.0234519 |
| spellingShingle | Huei-Chun Liu Wei-Che Lin Ming-Jang Chiu Cheng-Hsien Lu Chin-Yi Lin Shieh-Yueh Yang Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology. PLoS ONE |
| title | Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology. |
| title_full | Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology. |
| title_fullStr | Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology. |
| title_full_unstemmed | Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology. |
| title_short | Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology. |
| title_sort | development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology |
| url | https://doi.org/10.1371/journal.pone.0234519 |
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