Česká společnost pro hmotnostní spektrometrii

(CEEPC/IPM/CMSC 2022 - FrP-18)
Ion Mobility Mass Spectrometry Analysis of Aβ42 Oligomers

Mikuláš Vlk ^1,2 *, Martin Hubálek ¹, Josef Cvačka ^1,2

1. Institute of Organic Chemistry and Biochemistry of the CAS, Prague, Czech Republic
2. Department of Analytical Chemistry, Charles University, Prague, Czech Republic

Abstrakt

Amyloid beta is widely accepted as one of the main causes of Alzheimer’s disease (AD). Amyloid beta (1-42) and (1-40) are major components of senile plaques typically present in the grey matter of AD patients. Aβ(1-42) in β-sheet conformation forms a nucleation seed and promotes further aggregation of Aβ(1-40). Neurotoxic early stage oligomers aggregate into protofibrils and further prolongate to form mature fibrils and plaque deposits. Thorough characterization of soluble Aβ(1-42) oligomers is vital to comprehensive understanding of the oligomerization process. Native mass spectrometry can be utilized for such analysis as it combines using non-denaturing conditions with soft ionization techniques, therefore maintains non-covalent interactions. Optimization of experimental and instrumental conditions was preformed enabling detection of Aβ(1-42) oligomers formed in vitro. Moreover, ion mobility was used and optimized for separation of commonly occurring isobaric oligomer ions. Lower molecular weight oligomeric species up to hexamer (9 kDa – 27 kDa) were detected alongside the monomer.

* Korespondující autor: vlk.mikulas@gmail.com

Poděkování:

This work was conducted in collaboration with Alzheon, Inc.