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Development of an assay of plasma neurofilament light chain utilizing immunomagnetic reduction technology.
- Source :
-
PloS one [PLoS One] 2020 Jun 12; Vol. 15 (6), pp. e0234519. Date of Electronic Publication: 2020 Jun 12 (Print Publication: 2020). - Publication Year :
- 2020
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Abstract
- 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.<br />Competing Interests: Huei-Chun Liu, Chin-Yi Lin and Shieh-Yueh Yang are employees at MagQu Co., Ltd. Shieh-Yueh Yang is also an employee of MagQu LLC. Shieh-Yueh Yang owns stock in MagQu Co., Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.
- Subjects :
- Alzheimer Disease blood
Alzheimer Disease pathology
Axons metabolism
Axons pathology
Cognitive Dysfunction blood
Cognitive Dysfunction genetics
Cognitive Dysfunction pathology
Female
Humans
Immunomagnetic Separation
Intermediate Filaments genetics
Intermediate Filaments pathology
Male
Middle Aged
Parkinson Disease blood
Parkinson Disease genetics
Parkinson Disease pathology
Amyloid beta-Peptides blood
Biomarkers blood
Neurofilament Proteins blood
tau Proteins blood
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 15
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 32530970
- Full Text :
- https://doi.org/10.1371/journal.pone.0234519