Issue 46, 2022

An antibody scanning method for the detection of α-synuclein oligomers in the serum of Parkinson's disease patients

Abstract

Misfolded α-synuclein oligomers are closely implicated in the pathology of Parkinson's disease and related synucleinopathies. The elusive nature of these aberrant assemblies makes it challenging to develop quantitative methods to detect them and modify their behavior. Existing detection methods use antibodies to bind α-synuclein aggregates in biofluids, although it remains challenging to raise antibodies against α-synuclein oligomers. To address this problem, we used an antibody scanning approach in which we designed a panel of 9 single-domain epitope-specific antibodies against α-synuclein. We screened these antibodies for their ability to inhibit the aggregation process of α-synuclein, finding that they affected the generation of α-synuclein oligomers to different extents. We then used these antibodies to investigate the size distribution and morphology of soluble α-synuclein aggregates in serum and cerebrospinal fluid samples from Parkinson's disease patients. Our results indicate that the approach that we present offers a promising route for the development of antibodies to characterize soluble α-synuclein aggregates in biofluids.

Graphical abstract: An antibody scanning method for the detection of α-synuclein oligomers in the serum of Parkinson's disease patients

Supplementary files

Article information

Article type
Edge Article
Submitted
05 yan 2022
Accepted
16 sen 2022
First published
22 sen 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2022,13, 13815-13828

An antibody scanning method for the detection of α-synuclein oligomers in the serum of Parkinson's disease patients

K. Kulenkampff, D. Emin, R. Staats, Y. P. Zhang, L. Sakhnini, A. Kouli, O. Rimon, E. Lobanova, C. H. Williams-Gray, F. A. Aprile, P. Sormanni, D. Klenerman and M. Vendruscolo, Chem. Sci., 2022, 13, 13815 DOI: 10.1039/D2SC00066K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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