Stoichiometric Zn2+ interferes with the self-association of Aβ42: Insights from size distribution analysis.

The abnormal aggregation of amyloid β (Aβ) peptides in the brain has been recognized as a central event in Alzheimer's disease (AD). Divalent metal ions such as Zn2+ have been shown to be closely involved in modulating Aβ self-association. Although the link between Zn2+ dyshomeostasis and brain Aβ deposition has been established, the effect of Zn2+ on the aggregation of Aβ is still incompletely clarified. By combining analytical ultracentrifugation (AUC), circular dichroism (CD) spectroscopy, thioflavin T (ThT) assay and atomic force microscopy (AFM) imaging, we analyzed the impact of stoichiometric Zn2+ on the aggregation process of Aβ42, the main toxic isoform of Aβ species in the brain. Aβ42 aggregates found in the presence of Zn2+ were smaller in size, non-fibrillary and showed less β-sheet structures than aggregates formed in absence of Zn2+. AUC showed that Zn2+ was capable of retaining monomeric Aβ42 in solution. Zn2+ chelation by EDTA totally reversed the inhibitory effect of Zn2+ on Aβ42 fibrillation. Our results provide further evidence that Zn2+ shifts the self-association of Aβ42 toward a non-fibrillary pathway by interfering with the aggregation process at multiple levels.

• Publication year

  2018

• Venue

  International Journal of Biological Macromolecules

• Publication date

  2018-07-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.ijbiomac.2018.02.123PMID 29476859
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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