Mass and charge distributions of amyloid fibers involved in neurodegenerative diseases: mapping heterogeneity and polymorphism

Jonathan Pansieri (1) , Mohammad A. Halim (2) , Charlotte Vendrely (3) , Mireille Dumoulin (4) , François Legrand (4, 5) , Marcelle Moulin Sallanon (6) , Sabine Chierici (7) , Simona Denti (6) , Xavier Dagany (2) , Philippe Dugourd (2) , Christel Marquette (1) , Rodolphe Antoine (2) , Vincent Forge (1)

1 LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux
2 ILM - Institut Lumière Matière [Villeurbanne]
3 ERRMECe - Equipe de recherche sur les relations matrice extracellulaire-cellules
4 Laboratoire d'Enzymologie et Repliement des Protéines, Centre d'Ingénierie des Protéines
5 CRIG - Centre de Recherches des Instituts Groupés, Haute Ecole Libre Mosane
6 LRB - Radiopharmaceutiques biocliniques
7 DCM - Département de Chimie Moléculaire

Heterogeneity and polymorphism are generic features of amyloid fibers with some important effects on the related disease development. We report here the characterization, by charge detection mass spectrometry, of amyloid fibers made of three polypeptides involved in neurodegenerative diseases: A beta(1-42) peptide, tau and alpha-synuclein. Beside the mass of individual fibers, this technique enables to characterize the heterogeneity and the polymorphism of the population. In the case of A beta(1-42) peptide and tau protein, several coexisting species could be distinguished and characterized. In the case of alpha-synuclein, we show how the polymorphism affects the mass and charge distributions.

Domaines: Biochimie, Biologie Moléculaire; Neurosciences [q-bio.NC]

Jonathan Pansieri, Mohammad A. Halim, Charlotte Vendrely, Mireille Dumoulin, François Legrand, et al.. Mass and charge distributions of amyloid fibers involved in neurodegenerative diseases: mapping heterogeneity and polymorphism. Chemical Science, 2018, 9 (10), pp.2791-2796. ⟨10.1039/c7sc04542e⟩. ⟨hal-01793389⟩