title: In situ measurements of the formation and morphology of intracellular β-amyloid fibrils by super-resolution fluorescence imaging.
abstract: Misfolding and aggregation of peptides and proteins is a characteristic of many neurodegenerative disorders, including Alzheimer's disease (AD). In AD the β-amyloid peptide (Aβ) aggregates to form characteristic fibrillar structures, which are the deposits found as plaques in the brains of patients. We have used direct stochastic optical reconstruction microscopy, dSTORM, to probe the process of in situ Aβ aggregation and the morphology of the ensuing aggregates with a resolution better than 20 nm. We are able to distinguish different types of structures, including oligomeric assemblies and mature fibrils, and observe a number of morphological differences between the species formed in vitro and in vivo, which may be significant in the context of disease. Our data support the recent view that intracellular Aβ could be associated with Aβ pathogenicity in AD, although the major deposits are extracellular, and suggest that this approach will be widely applicable to studies of the molecular mechanisms of protein deposition diseases.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Pembroke Street, Cambridge CB2 3RA, UK.
authors.forename: Gabriele S
authors.initials: GS
authors.lastname: Kaminski Schierle
authors.forename: Sebastian
authors.initials: S
authors.lastname: van de Linde
authors.forename: Miklos
authors.initials: M
authors.lastname: Erdelyi
authors.forename: Elin K
authors.initials: EK
authors.lastname: Esbjörner
authors.forename: Teresa
authors.initials: T
authors.lastname: Klein
authors.forename: Eric
authors.initials: E
authors.lastname: Rees
authors.forename: Carlos W
authors.initials: CW
authors.lastname: Bertoncini
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.forename: Markus
authors.initials: M
authors.lastname: Sauer
authors.forename: Clemens F
authors.initials: CF
authors.lastname: Kaminski
mesh_terms: D000544:Alzheimer Disease; D000682:Amyloid / Q000096:biosynthesis* / Q000737:chemistry* / Q000648:ultrastructure; D002460:Cell Line; D006801:Humans; D008722:Methods; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence / Q000379:methods*
chemical_list: D000682:Amyloid