TY - JOUR
T1 - α-Synuclein plastic antibody applied to monitor monomeric structures and discriminate aggregated forms in human CSF
AU - da Silva, Inês S
AU - Cardoso, Ana R
AU - Reimer, Lasse
AU - König, Annekatrin
AU - van Riesen, Christoph
AU - Outeiro, Tiago Fleming
AU - Jensen, Poul Henning
AU - Sales, M Goreti F
N1 - Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2025/1/15
Y1 - 2025/1/15
N2 - Aggregation 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.
AB - Aggregation 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.
KW - Antibodies, Immobilized/chemistry
KW - Antibodies/chemistry
KW - Biosensing Techniques/methods
KW - Dielectric Spectroscopy/methods
KW - Electrochemical Techniques/methods
KW - Electrodes
KW - Humans
KW - Limit of Detection
KW - Methylene Blue/chemistry
KW - Parkinson Disease/cerebrospinal fluid
KW - Protein Aggregates
KW - alpha-Synuclein/cerebrospinal fluid
UR - http://www.scopus.com/inward/record.url?scp=85208105636&partnerID=8YFLogxK
U2 - 10.1016/j.bios.2024.116880
DO - 10.1016/j.bios.2024.116880
M3 - Journal article
C2 - 39509995
SN - 0956-5663
VL - 268
SP - 116880
JO - Biosensors and Bioelectronics
JF - Biosensors and Bioelectronics
M1 - 116880
ER -