Single-Chain Variable Fragments Targeting Plasma Exosome Amyloid-β Peptide Subtypes for Diagnosis of Alzheimer’s Disease
- 1State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 211189, China
Abstract
The diagnostic value of the Aβ1-42/Aβ1-40 ratio in peripheral blood as a biomarker for Alzheimer’s disease (AD) remains a subject of considerable interest. However, this ratio in plasma exosomes is still underestimated. To investigate the potential clinical performances, this study has established a chemiluminescence immunoassay (CLIA) for the specific detection of Aβ1-42 and Aβ1-40 in plasma exosomes using single-chain variable fragments (scFv). Plasma samples from 20 AD patients and 20 non-AD individuals were detected by the established scFv-based CLIA, with the traditional monoclonal antibody (mAb)-based CLIA as the reference method. The results demonstrated that the plasma exosome Aβ1-42/Aβ1-40 ratio in AD patients (0.70 ± 0.35) was significantly lower than that in the non-AD control group (1.82 ± 0.79, p < 0.001). In comparison with the mAb-based assay, the scFv-based CLIA exhibited superior analytical performance, with a lower limit of detection (1 pg/mL vs. 50 pg/mL) and higher specificity (cross-reactivity rate < 5%). When the Aβ1-42/Aβ1-40 ratio of 1.075 was set as the cutoff value, the scFv-based assay achieved a diagnostic sensitivity of 90.0%, which was numerically higher than that of the mAb-based assay (85.0%), with comparable specificity (90.0% vs. 90.0%). Generally, this study has developed a highly sensitive and specific scFv-based method for the detection of plasma exosome Aβ subtypes, which supports that the plasma exosome Aβ1-42/Aβ1-40 ratio is a potential non-invasive biomarker for differentiating clinically diagnosed AD from non-AD controls in this pilot cohort.
Related
- Alzheimer’s disease diagnosis based on gene selection and cross-tissue validation
- Advancing Alzheimer's Disease Treatment: Synergistic Ligand Combinations Targeting BACE1 via Multi-Ligand Simultaneous Docking
- Polyaniline-gold nanoparticle-based biosensor targeting miR-21-5p for early diagnosis of leptospirosis
- RNA:DNA hybrids from Okazaki fragments contribute to establish the Ku-mediated barrier to replication-fork degradation
- Precision meets scale: DSB- and recombinase-free targeted insertion of large DNA fragments
BibTeX
@article{zhou2026singlechain,
title = {{Single-Chain Variable Fragments Targeting Plasma Exosome Amyloid-β Peptide Subtypes for Diagnosis of Alzheimer’s Disease}},
author = {Xiaojin Zhou and Zan Wang and Hui Jiang},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms272110006},
url = {https://www.mdpi.com/1422-0067/27/21/10006},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-Chain Variable Fragments Targeting Plasma Exosome Amyloid-β Peptide Subtypes for Diagnosis of Alzheimer’s Disease
AU - Xiaojin Zhou
AU - Zan Wang
AU - Hui Jiang
PY - 2026
DA - 2026/11/08
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms272110006
UR - https://www.mdpi.com/1422-0067/27/21/10006
AB - The diagnostic value of the Aβ1-42/Aβ1-40 ratio in peripheral blood as a biomarker for Alzheimer’s disease (AD) remains a subject of considerable interest. However, this ratio in plasma exosomes is still underestimated. To investigate the potential clinical performances, this study has established a chemiluminescence immunoassay (CLIA) for the specific detection of Aβ1-42 and Aβ1-40 in plasma exosomes using single-chain variable fragments (scFv). Plasma samples from 20 AD patients and 20 non-AD individuals were detected by the established scFv-based CLIA, with the traditional monoclonal antibody (mAb)-based CLIA as the reference method. The results demonstrated that the plasma exosome Aβ1-42/Aβ1-40 ratio in AD patients (0.70 ± 0.35) was significantly lower than that in the non-AD control group (1.82 ± 0.79, p < 0.001). In comparison with the mAb-based assay, the scFv-based CLIA exhibited superior analytical performance, with a lower limit of detection (1 pg/mL vs. 50 pg/mL) and higher specificity (cross-reactivity rate < 5%). When the Aβ1-42/Aβ1-40 ratio of 1.075 was set as the cutoff value, the scFv-based assay achieved a diagnostic sensitivity of 90.0%, which was numerically higher than that of the mAb-based assay (85.0%), with comparable specificity (90.0% vs. 90.0%). Generally, this study has developed a highly sensitive and specific scFv-based method for the detection of plasma exosome Aβ subtypes, which supports that the plasma exosome Aβ1-42/Aβ1-40 ratio is a potential non-invasive biomarker for differentiating clinically diagnosed AD from non-AD controls in this pilot cohort.
SN - 1422-0067
ER -