title: Single point mutations induce a switch in the molecular mechanism of the aggregation of the Alzheimer's disease associated Aβ42 peptide.
abstract: Single point mutations in the Alzheimer's disease associated Aβ42 peptide are found to alter significantly its neurotoxic properties in vivo and have been associated with early onset forms of this devastating condition. We show that such mutations can induce structural changes in Aβ42 fibrils and are associated with a dramatic switch in the fibril-dependent mechanism by which Aβ42 aggregates. These observations reveal how subtle perturbations to the physicochemical properties of the Aβ peptide, and the structural properties of fibrils that it forms, can have profound effects on the mechanism of its aggregation and pathogenicity.
authors.affiliation: Department of Chemistry, University of Cambridge , Lensfield Road, Cambridge, CB2 1EW, United Kingdom.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bolognesi
authors.forename: Samuel I A
authors.initials: SI
authors.lastname: Cohen
authors.forename: Pablo
authors.initials: P
authors.lastname: Aran Terol
authors.forename: Elin K
authors.initials: EK
authors.lastname: Esbjörner
authors.forename: Sofia
authors.initials: S
authors.lastname: Giorgetti
authors.forename: Maria F
authors.initials: MF
authors.lastname: Mossuto
authors.forename: Antonino
authors.initials: A
authors.lastname: Natalello
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Brorsson
authors.forename: Tuomas P J
authors.initials: TP
authors.lastname: Knowles
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.forename: Leila M
authors.initials: LM
authors.lastname: Luheshi
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D017354:Point Mutation; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)