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

Inês S da Silva; Ana R Cardoso; Lasse Reimer; Annekatrin König; Christoph van Riesen; Tiago Fleming Outeiro; Poul Henning Jensen; M Goreti F Sales

doi:10.1016/j.bios.2024.116880

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

Inês S da Silva, Ana R Cardoso, Lasse Reimer, Annekatrin König, Christoph van Riesen, Tiago Fleming Outeiro, Poul Henning Jensen, M Goreti F Sales

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

1 Citation (Scopus)

Abstract

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.

Original language	English
Article number	116880
Journal	Biosensors and Bioelectronics
Volume	268
Pages (from-to)	116880
ISSN	0956-5663
DOIs	https://doi.org/10.1016/j.bios.2024.116880
Publication status	Published - 15 Jan 2025

Keywords

Antibodies, Immobilized/chemistry
Antibodies/chemistry
Biosensing Techniques/methods
Dielectric Spectroscopy/methods
Electrochemical Techniques/methods
Electrodes
Humans
Limit of Detection
Methylene Blue/chemistry
Parkinson Disease/cerebrospinal fluid
Protein Aggregates
alpha-Synuclein/cerebrospinal fluid
Parkinson's disease
Plastic antibody
Carbon screen-printed electrodes
Electrochemical biosensor
Alpha-synuclein

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

abstract = "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.",

keywords = "Antibodies, Immobilized/chemistry, Antibodies/chemistry, Biosensing Techniques/methods, Dielectric Spectroscopy/methods, Electrochemical Techniques/methods, Electrodes, Humans, Limit of Detection, Methylene Blue/chemistry, Parkinson Disease/cerebrospinal fluid, Protein Aggregates, alpha-Synuclein/cerebrospinal fluid, Parkinson's disease, Plastic antibody, Carbon screen-printed electrodes, Electrochemical biosensor, Alpha-synuclein",

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year = "2025",

month = jan,

day = "15",

doi = "10.1016/j.bios.2024.116880",

language = "English",

volume = "268",

pages = "116880",

journal = "Biosensors and Bioelectronics",

issn = "0956-5663",

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α-Synuclein plastic antibody applied to monitor monomeric structures and discriminate aggregated forms in human CSF. / da Silva, Inês S; Cardoso, Ana R; Reimer, Lasse et al.
In: Biosensors and Bioelectronics, Vol. 268, 116880, 15.01.2025, p. 116880.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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

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

KW - Parkinson's disease

KW - Plastic antibody

KW - Carbon screen-printed electrodes

KW - Electrochemical biosensor

KW - Alpha-synuclein

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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 -

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

Abstract

Keywords

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