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

Abstract

Misfolded alpha-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 toxic behavior. Many existing detection methods use antibodies to bind alpha-synuclein aggregates in biofluids, although it remains challenging to raise antibodies against alpha-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 alpha-synuclein. We screened these antibodies for their ability to inhibit the aggregation process of alpha-synuclein, finding that they affected the generation of a-synuclein oligomers to different extents.  We then used these antibodies to investigate the size distribution and morphology of soluble alpha-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 alpha-synuclein aggregates in biofluids.

Article information

Article type
Edge Article
Submitted
05 Jan 2022
Accepted
16 Sep 2022
First published
22 Sep 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, Accepted Manuscript

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

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

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