Stoichiometric Zn 2+ interferes with the self-association of Aβ42: Insights from size distribution analysis

Zhang, Tao; Nagel-Steger, Luitgard; Pauly, Thomas

doi:10.1016/j.ijbiomac.2018.02.123

Journal Article

FZJ-2018-01403

Stoichiometric Zn 2+ interferes with the self-association of Aβ42: Insights from size distribution analysis

Zhang, T.FZJ* ; Pauly, T. ; Nagel-Steger, L. (Corresponding author)FZJ*

2018
Elsevier New York, NY [u.a.]

International journal of biological macromolecules 113, 631-639 (2018) [10.1016/j.ijbiomac.2018.02.123]

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Abstract: 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.

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