In vitro oligomerization and fibrillogenesis of Amyloid-beta peptides

Núria Benseny-Cases, Oksana Klementieva, Josep Cladera*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

24 Citations (Scopus)


© 2012 Springer Science+Business Media Dordrecht. The amyloid beta Aβ(1–40) and Aβ(1–42) peptides are the main components of the fibrillar plaques characteristically found in the brains affected by Alzheimer’s disease. Fibril formation has been thoroughly studied in vitro using synthetic amyloid peptides and has been described to be a nucleation dependent polymerization process. During this process, defined by a slow nucleation phase followed by a rapid exponential elongation reaction, a whole range of aggregated species (low and high molecular weight aggregates) precede fibril formation. Toxic species related to the onset and development of Alzheimer’s disease are thought to be found among these prefibrillar aggregates. Two main procedures are used to experimentally monitor fibril formation kinetics: through the measurement of the light scattered by the different peptide aggregates and using the fluorescent dye thioflavin T, which fluorescence increases when specifically interacting with amyloid fibrils. Reproducibility may, however, be difficult to achieve when measuring and characterizing fibril formation kinetics. This fact is mainly due to the difficulty in experimentally handling amyloid peptides, which is directly related to the difficulty of having them in a monomeric form at the beginning of the polymerization process. This has to do mainly with the type of solvent used for the preparation of the peptide stock solutions (water, DMSO, TFE, HFIP) and the control of determinant physicochemical parameters such as pH. Moreover, kinetic progression turns out to be highly dependent on the type of peptide counter-ion used, which will basically determine the duration of the nucleation phase and the rate at which high molecular weight oligomers are formed. Centrifugation and filtration procedures used in the preparation of the peptide stock solutions will also greatly influence the duration of the fibril formation process. In this chapter, a survey of the alluded experimental procedures is provided and a general frame is proposed for the interpretation of the fibril formation kinetics, intended to integrate the results from the different experimental approaches. The significance of the different aggregated species in terms of cell toxicity will be discussed. Special emphasis will be given to the influence of pH on the structural and toxic characteristics of amyloid aggregates, an aspect that may be particularly relevant in some specific physiological conditions.
Original languageEnglish
Pages (from-to)53-74
JournalSubcellular Biochemistry
Publication statusPublished - 29 May 2012


  • Amyloid beta (Aβ)
  • Aβ stock solutions
  • Fibrillogenesis
  • Oligomerization
  • Toxicity


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