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Heavy metals toxicity: effect of cadmium ions on amyloid beta protein 1–42. Possible implications for Alzheimer’s disease

Abstract

Cadmium (Cd) is an environmental contaminant, highly toxic to humans. This biologically non-essential element accumulates in the body, especially in the kidney, liver, lung and brain and can induce several toxic effects, depending on the concentration and the exposure time. Cd has been linked to Alzheimer’s disease (AD) as a probable risk factor, as it shows higher concentrations in brain tissues of AD patients than in healthy people, its implication in the formation of neurofibrillary tangles and in the aggregation process of amyloid beta peptides (AβPs). AβPs seem to have toxic properties, particularly in their aggregated state; insoluble AβP forms, such as small and large aggregates, protofibrils and fibrils, appear to be implicated in the pathogenesis of AD. In our study, we have evaluated the effect of Cd, at different concentrations, both on the AβP1–42 ion channel incorporated in a planar lipid membrane made up of phosphatidylcholine containing 30 % cholesterol and on the secondary structure of AβP1–42 in aqueous environment. Cadmium is able to interact with the AβP1–42 peptide by acting on the channel incorporated into the membrane as well as on the peptide in solution, both decreasing AβP1–42 channel frequency and in solution forming large and amorphous aggregates prone to precipitate. These experimental observations suggesting a toxic role for Cd strengthen the hypothesis that Cd may interact directly with AβPs and may be a risk factor in AD.

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Acknowledgments

This work was supported by a grant from the Fondazione Cassa di Risparmio di Puglia. The authors acknowledge Anthony Green for proofreading and providing linguistic advice.

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Correspondence to Daniela Meleleo.

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Notarachille, G., Arnesano, F., Calò, V. et al. Heavy metals toxicity: effect of cadmium ions on amyloid beta protein 1–42. Possible implications for Alzheimer’s disease. Biometals 27, 371–388 (2014). https://doi.org/10.1007/s10534-014-9719-6

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Keywords

  • Cadmium
  • AβP
  • Aggregation
  • Ion channel
  • Membranes