Stabilization of α-synuclein oligomers using formaldehyde

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  • Harm Ruesink, Danish Research Institute of Translational Neuroscience - DANDRITE, Aarhus University, Aarhus, Denmark., NEURODIN; Department of Biomedicine; Aarhus University; Aarhus, Denmark; Neuroimmunology of Degenerative Diseases group; Department of Biomedicine; Aarhus University; Aarhus, Denmark.
  • ,
  • Lasse Reimer
  • Emil Gregersen
  • Arne Moeller
  • Cristine Betzer
  • Poul Henning Jensen

The group of neurodegenerative diseases, Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) all exhibit inclusions containing amyloid-type α-synuclein (α-syn) aggregates within degenerating brain cells. α-syn also exists as soluble oligomeric species that are hypothesized to represent intermediates between its native and aggregated states. These oligomers are present in brain extracts from patients suffering from synucleinopathies and hold great potential as biomarkers. Although easily prepared in vitro, oligomers are metastable and dissociate over time, thereby complicating α-syn oligomer research. Using the small amine-reactive cross-linker, formaldehyde (FA), we successfully stabilized α-syn oligomers without affecting their size, overall structure or antigenicity towards aggregate-conformation specific α-syn antibodies FILA and MJFR-14-6-4-2. Further, cross-linked α-syn oligomers show resistance towards denaturant like urea and SDS treatment and remain fully functional as internal standard in an aggregation-specific enzyme-linked immunosorbent assay (ELISA) despite prior incubation with urea. We propose that FA cross-linked α-syn oligomers could serve as important calibrators to facilitate comparative and standardized α-syn biomarker studies going forward.

Original languageEnglish
JournalPLOS ONE
Volume14
Issue10
Pages (from-to)e0216764
ISSN1932-6203
DOIs
Publication statusPublished - 2019
Externally publishedYes

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