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

Published version
Peer-reviewed

Type

Article

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Authors

Emin, Derya 
Staats, Roxine 
Zhang, Yu P 
Sakhnini, Laila 

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.

Description

Keywords

3401 Analytical Chemistry, 34 Chemical Sciences, Neurodegenerative, Aging, Parkinson's Disease, Brain Disorders, Neurosciences, Acquired Cognitive Impairment, Biotechnology, 2 Aetiology, 2.1 Biological and endogenous factors, Neurological

Journal Title

Chem Sci

Conference Name

Journal ISSN

2041-6520
2041-6539

Volume Title

13

Publisher

Royal Society of Chemistry (RSC)
Sponsorship
European Research Council (669237)
Medical Research Council (MR/R007446/1)
European Commission (201461)