title: Identification of distinct physiochemical properties of toxic prefibrillar species formed by Aβ peptide variants.
abstract: The formation of amyloid-β peptide (Aβ) aggregates at an early stage during the self-assembly process is an important factor in the development of Alzheimer's disease. The toxic effect is believed to be exerted by prefibrillar species of Aβ. It is therefore important to identify which prefibrillar species are toxic and characterize their distinct properties. In the present study, we investigated the in vitro aggregation behavior of Aβ-derived peptides possessing different levels of neurotoxic activity, using fluorescence spectroscopy in combination with transmission electron microscopy. The toxicity of various Aβ aggregates was assessed by using cultures of human neuroblastoma cells. Through combined use of the fluorescence probe 8-anilino-1-napthalenesulfonate (ANS) and the novel luminescent probe pentamer formyl thiophene acetic acid (p-FTAA), we were able to identify those Aβ peptide-derived prefibrillar species which exhibited cellular toxicity. In particular, species, which formed early during the aggregation process and showed strong p-FTAA and ANS fluorescence, were the species that possessed toxic activities. Moreover, by manipulating the aggregation conditions, it was possible to change the capacity of the Aβ peptide to form nontoxic versus toxic species.
authors.affiliation: Division of Molecular Biotechnology, Department of Physics, Chemistry and Biology, Linköping University, Sweden. anngo@ifm.liu.se
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Göransson
authors.forename: K Peter R
authors.initials: KP
authors.lastname: Nilsson
authors.forename: Katarina
authors.initials: K
authors.lastname: Kågedal
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Brorsson
mesh_terms: D000085:Acetates / Q000737:chemistry; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity*; D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D002460:Cell Line; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments / Q000737:chemistry* / Q000633:toxicity*; D013876:Thiophenes / Q000737:chemistry
chemical_list: C515594:8-anilino-1-naphthalenesulfonic acid; D000085:Acetates; D016229:Amyloid beta-Peptides; D000817:Anilino Naphthalenesulfonates; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D013876:Thiophenes; C075222:amyloid beta-protein (1-42); C572917:pentamer formyl thiophene acetic acid