Validation of a newly developed immunoassay for TDP-43 in human plasma
The level of TAR DNA-binding protein 43 (TDP-43) in human blood was reported to have potential for use as a specific fluid biomarker, which represents disease-specific pathologies, for TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD),...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-01-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024007035 |
| _version_ | 1827360837859278848 |
|---|---|
| author | Sayo Matsuura Harutsugu Tatebe Makoto Higuchi Takahiko Tokuda |
| author_facet | Sayo Matsuura Harutsugu Tatebe Makoto Higuchi Takahiko Tokuda |
| author_sort | Sayo Matsuura |
| collection | DOAJ |
| description | The level of TAR DNA-binding protein 43 (TDP-43) in human blood was reported to have potential for use as a specific fluid biomarker, which represents disease-specific pathologies, for TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), which involves the aggregation and deposition of TDP-43 in the nervous system. However, at present, no reliable immunoassay can precisely quantify TDP-43 in human plasma and detect the difference in plasma TDP-43 levels between patients with ALS and controls. We recently developed a novel ultrasensitive immunoassay to quantify TDP-43 in human plasma, and in this study, we analytically validated this assay for application as a diagnostic biomarker for TDP-43 proteinopathies. The novel TDP-43 assay was assessed for the limit of detection, lower limit of quantification, intra- and interassay variation, linearity, parallelism, and analytical spike recoveries. Additionally, 17 pilot plasma samples obtained from patients with ALS and age-matched controls were analyzed using the assay. Our novel TDP-43 assay showed sufficient analytical performance to quantify TDP-43 in human plasma, with high sensitivity (LOD and LLOQ of 0.109 and 0.759 pg/mL, respectively) and high intra- and interassay precision (%CV) below 15 %. The experimental results for spike recovery, parallelism, and dilution linearity were also acceptable. In addition, despite a small sample size, significant differences in the plasma levels of TDP-43 were found between patients with ALS and controls (ALS, 66.63 ± 20.52 pg/mL; control, 42.70 ± 23.06 pg/mL, p = 0.0330). These results support that our novel TDP-43 assay is a reliable and innovative method for the quantification of TDP-43 in human plasma and can be a potential blood-based biomarker for the diagnosis of TDP-43 proteinopathies. Further large-scale studies are warranted to validate its usefulness. |
| first_indexed | 2024-03-08T06:55:10Z |
| format | Article |
| id | doaj.art-9c46ca2f42b64796a90c49ab0959c0e7 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T06:55:10Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-9c46ca2f42b64796a90c49ab0959c0e72024-02-03T06:38:11ZengElsevierHeliyon2405-84402024-01-01102e24672Validation of a newly developed immunoassay for TDP-43 in human plasmaSayo Matsuura0Harutsugu Tatebe1Makoto Higuchi2Takahiko Tokuda3Department of Functional Brain Imaging, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Chiba, 263-8555, JapanDepartment of Functional Brain Imaging, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Chiba, 263-8555, JapanDepartment of Functional Brain Imaging, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Chiba, 263-8555, JapanCorresponding author. Inage-ku, Chiba-shi, Chiba, 263-8555, Japan.; Department of Functional Brain Imaging, Institute for Quantum Medical Science, Quantum Life and Medical Science Directorate, National Institutes for Quantum Science and Technology, Chiba, 263-8555, JapanThe level of TAR DNA-binding protein 43 (TDP-43) in human blood was reported to have potential for use as a specific fluid biomarker, which represents disease-specific pathologies, for TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), which involves the aggregation and deposition of TDP-43 in the nervous system. However, at present, no reliable immunoassay can precisely quantify TDP-43 in human plasma and detect the difference in plasma TDP-43 levels between patients with ALS and controls. We recently developed a novel ultrasensitive immunoassay to quantify TDP-43 in human plasma, and in this study, we analytically validated this assay for application as a diagnostic biomarker for TDP-43 proteinopathies. The novel TDP-43 assay was assessed for the limit of detection, lower limit of quantification, intra- and interassay variation, linearity, parallelism, and analytical spike recoveries. Additionally, 17 pilot plasma samples obtained from patients with ALS and age-matched controls were analyzed using the assay. Our novel TDP-43 assay showed sufficient analytical performance to quantify TDP-43 in human plasma, with high sensitivity (LOD and LLOQ of 0.109 and 0.759 pg/mL, respectively) and high intra- and interassay precision (%CV) below 15 %. The experimental results for spike recovery, parallelism, and dilution linearity were also acceptable. In addition, despite a small sample size, significant differences in the plasma levels of TDP-43 were found between patients with ALS and controls (ALS, 66.63 ± 20.52 pg/mL; control, 42.70 ± 23.06 pg/mL, p = 0.0330). These results support that our novel TDP-43 assay is a reliable and innovative method for the quantification of TDP-43 in human plasma and can be a potential blood-based biomarker for the diagnosis of TDP-43 proteinopathies. Further large-scale studies are warranted to validate its usefulness.http://www.sciencedirect.com/science/article/pii/S2405844024007035TDP-43Plasma biomarkerImmunoassayValidationAmyotrophic lateral sclerosis |
| spellingShingle | Sayo Matsuura Harutsugu Tatebe Makoto Higuchi Takahiko Tokuda Validation of a newly developed immunoassay for TDP-43 in human plasma Heliyon TDP-43 Plasma biomarker Immunoassay Validation Amyotrophic lateral sclerosis |
| title | Validation of a newly developed immunoassay for TDP-43 in human plasma |
| title_full | Validation of a newly developed immunoassay for TDP-43 in human plasma |
| title_fullStr | Validation of a newly developed immunoassay for TDP-43 in human plasma |
| title_full_unstemmed | Validation of a newly developed immunoassay for TDP-43 in human plasma |
| title_short | Validation of a newly developed immunoassay for TDP-43 in human plasma |
| title_sort | validation of a newly developed immunoassay for tdp 43 in human plasma |
| topic | TDP-43 Plasma biomarker Immunoassay Validation Amyotrophic lateral sclerosis |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024007035 |
| work_keys_str_mv | AT sayomatsuura validationofanewlydevelopedimmunoassayfortdp43inhumanplasma AT harutsugutatebe validationofanewlydevelopedimmunoassayfortdp43inhumanplasma AT makotohiguchi validationofanewlydevelopedimmunoassayfortdp43inhumanplasma AT takahikotokuda validationofanewlydevelopedimmunoassayfortdp43inhumanplasma |