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. ORCID: https://orcid.org/0000-0002-3126-1903, Kouli, Antonina, Williams-Gray, Caroline H. and Klenerman, David 2023. Imaging protein aggregates in Parkinson’s Disease serum using aptamer-assisted single-molecule pull-down. Analytical Chemistry 95 (41) , pp. 15254-15263. 10.1021/acs.analchem.3c02515

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: https://creativecommons.org/licenses/by/4.0/, Start Date: 2023-10-02
Publisher:	American Chemical Society
ISSN:	0003-2700
Date of First Compliant Deposit:	24 October 2023
Date of Acceptance:	18 September 2023
Last Modified:	24 Oct 2023 09:15
URI:	https://orca.cardiff.ac.uk/id/eprint/163446

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