title: Ion mobility separation coupled with MS detects two structural states of Alzheimer's disease Aβ1-40 peptide oligomers.
abstract: Mounting evidence points to the soluble oligomers of amyloid β (Aβ) peptide as important neurotoxic species in Alzheimer's disease, causing synaptic dysfunction and neuronal injury, and finally leading to neuronal death. The mechanism of the Aβ peptide self-assembly is still under debate. Here, Aβ1-40 peptide oligomers were studied using mass spectrometry combined with ion mobility spectrometry, which allowed separation of the signals of numerous oligomers and measurement of their collisional cross-section values (Ω). For several oligomers, at least two different species of different Ω values were detected, indicating the presence of at least two families of conformers: compact and extended. The obtained results are rationalized by a set of molecular models of Aβ1-40 oligomer structure that provided a very good correlation between the experimental and theoretical Ω values, both for the compact and the extended forms. Our results indicate that mass spectrometry detects oligomeric species that are on-pathway in the process of fibril formation or decay, but also alternative structures which may represent off-pathway evolution of oligomers.
authors.affiliation: Department of Biophysics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kłoniecki
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jabłonowska
authors.forename: Jarosław
authors.initials: J
authors.lastname: Poznański
authors.forename: James
authors.initials: J
authors.lastname: Langridge
authors.forename: Chris
authors.initials: C
authors.lastname: Hughes
authors.forename: Iain
authors.initials: I
authors.lastname: Campuzano
authors.forename: Kevin
authors.initials: K
authors.lastname: Giles
authors.forename: Michał
authors.initials: M
authors.lastname: Dadlez
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism*; D010957:Plasmids; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments