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α-Synuclein plastic antibody applied to monitor monomeric structures and discriminate aggregated forms in human CSF

Lookup NU author(s): Professor Tiago OuteiroORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© 2024 The AuthorsAggregation of alpha-synuclein (aSyn) occurs in presynaptic neurons and constitutes a key factor for the progression of Parkinson's disease, emphasising the urgency of early detection to support effective treatment. Unfortunately, a reliable, sensitive and cost-effective diagnostic tool has so far been lacking. Thus, this work presents a novel biosensor for detecting aSyn using plastic antibodies coupled to electrochemical detection. This biosensor was designed for portability and compatibility with point-of-care devices and exploits the electropolymerization of methylene blue (MB) together with aSyn on the carbon working electrode of screen-printed electrodes (SPEs). By electrochemical impedance spectroscopy (EIS) measurements, the sensor showed exceptional analytical performance in detecting aSyn monomers in human CSF samples. It showed a linear trend of response from 1 fM to 10 pM with an impressively low limit of detection of 69 aM. Selectivity tests confirmed the predominant response to aSyn monomers, a less intense response to oligomers and insensitivity to fibrils. Overall, this plastic antibody-based electrochemical sensor represents a significant breakthrough as it is the first of its kind to accurately, sensitively and selectively detect aSyn monomers with a partial response to oligomers. Its simplicity and reproducibility promise to contribute to the early and effective diagnosis of Parkinson's disease.


Publication metadata

Author(s): da Silva IS, Cardoso AR, Reimer L, Konig A, van Riesen C, Outeiro TF, Jensen PH, Sales MGF

Publication type: Article

Publication status: Published

Journal: Biosensors and Bioelectronics

Year: 2025

Volume: 268

Print publication date: 15/01/2025

Online publication date: 06/11/2024

Acceptance date: 24/10/2024

Date deposited: 19/11/2024

ISSN (print): 0956-5663

ISSN (electronic): 1873-4235

Publisher: Elsevier Ltd

URL: https://doi.org/10.1016/j.bios.2024.116880

DOI: 10.1016/j.bios.2024.116880

Data Access Statement: No data was used for the research described in the article.


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Funding

Funder referenceFunder name
825664
BMBF
Deutsche Forschungsgemeinschaft
ERA-Net
EU Joint Programme – Neurodegenerative Disease Research (JPND)
EXC 2067/1–390729940
JPCOFUND2
JPCOFUND2/0001/2019
National Foundation for Science and Technology
SFB1286 (B8)

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