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Imaging Protein Aggregates in Parkinson’s Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down

[Image: see text] The formation of soluble α-synuclein (α-syn) and amyloid-β (Aβ) aggregates is associated with the development of Parkinson’s disease (PD). Current methods mainly focus on the measurement of the aggregate concentration and are unable to determine their heterogeneous size and shape,...

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Autores principales: Zhang, Yu P., Lobanova, Evgeniia, Emin, Derya, Lobanov, Sergey V., Kouli, Antonina, Williams-Gray, Caroline H., Klenerman, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585954/
https://www.ncbi.nlm.nih.gov/pubmed/37782556
http://dx.doi.org/10.1021/acs.analchem.3c02515
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author Zhang, Yu P.
Lobanova, Evgeniia
Emin, Derya
Lobanov, Sergey V.
Kouli, Antonina
Williams-Gray, Caroline H.
Klenerman, David
author_facet Zhang, Yu P.
Lobanova, Evgeniia
Emin, Derya
Lobanov, Sergey V.
Kouli, Antonina
Williams-Gray, Caroline H.
Klenerman, David
author_sort Zhang, Yu P.
collection PubMed
description [Image: see text] The formation of soluble α-synuclein (α-syn) and amyloid-β (Aβ) aggregates is associated with the development of Parkinson’s disease (PD). Current methods mainly focus on the measurement of the aggregate concentration and are unable to determine their heterogeneous size and shape, which potentially also change during the development of PD due to increased protein aggregation. In this work, we introduce aptamer-assisted single-molecule pull-down (APSiMPull) combined with super-resolution fluorescence imaging of α-syn and Aβ aggregates in human serum from early PD patients and age-matched controls. Our diffraction-limited imaging results indicate that the proportion of α-syn aggregates (α-syn/(α-syn+Aβ)) can be used to distinguish PD and control groups with an area under the curve (AUC) of 0.85. Further, super resolution fluorescence imaging reveals that PD serums have a higher portion of larger and rounder α-syn aggregates than controls. Little difference was observed for Aβ aggregates. Combining these two metrics, we constructed a new biomarker and achieved an AUC of 0.90. The combination of the aggregate number and morphology provides a new approach to early PD diagnosis.
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spelling pubmed-105859542023-10-20 Imaging Protein Aggregates in Parkinson’s Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down Zhang, Yu P. Lobanova, Evgeniia Emin, Derya Lobanov, Sergey V. Kouli, Antonina Williams-Gray, Caroline H. Klenerman, David Anal Chem [Image: see text] The formation of soluble α-synuclein (α-syn) and amyloid-β (Aβ) aggregates is associated with the development of Parkinson’s disease (PD). Current methods mainly focus on the measurement of the aggregate concentration and are unable to determine their heterogeneous size and shape, which potentially also change during the development of PD due to increased protein aggregation. In this work, we introduce aptamer-assisted single-molecule pull-down (APSiMPull) combined with super-resolution fluorescence imaging of α-syn and Aβ aggregates in human serum from early PD patients and age-matched controls. Our diffraction-limited imaging results indicate that the proportion of α-syn aggregates (α-syn/(α-syn+Aβ)) can be used to distinguish PD and control groups with an area under the curve (AUC) of 0.85. Further, super resolution fluorescence imaging reveals that PD serums have a higher portion of larger and rounder α-syn aggregates than controls. Little difference was observed for Aβ aggregates. Combining these two metrics, we constructed a new biomarker and achieved an AUC of 0.90. The combination of the aggregate number and morphology provides a new approach to early PD diagnosis. American Chemical Society 2023-10-02 /pmc/articles/PMC10585954/ /pubmed/37782556 http://dx.doi.org/10.1021/acs.analchem.3c02515 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Zhang, Yu P.
Lobanova, Evgeniia
Emin, Derya
Lobanov, Sergey V.
Kouli, Antonina
Williams-Gray, Caroline H.
Klenerman, David
Imaging Protein Aggregates in Parkinson’s Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down
title Imaging Protein Aggregates in Parkinson’s Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down
title_full Imaging Protein Aggregates in Parkinson’s Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down
title_fullStr Imaging Protein Aggregates in Parkinson’s Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down
title_full_unstemmed Imaging Protein Aggregates in Parkinson’s Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down
title_short Imaging Protein Aggregates in Parkinson’s Disease Serum Using Aptamer-Assisted Single-Molecule Pull-Down
title_sort imaging protein aggregates in parkinson’s disease serum using aptamer-assisted single-molecule pull-down
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10585954/
https://www.ncbi.nlm.nih.gov/pubmed/37782556
http://dx.doi.org/10.1021/acs.analchem.3c02515
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