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Copper Enhances Amyloid-β Peptide Neurotoxicity and non β-Aggregation: A Series of Experiments Conducted upon Copper-Bound and Copper-Free Amyloid-β Peptide

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Abstract

Alzheimer’s disease is characterized by the abnormal aggregation of amyloid-β peptide (Aβ) in extracellular deposits known as senile plaques. However, the nature of the toxic Aβ species and its precise mechanism of action remain unclear. Previous reports suggest that the histidine residues are involved in copper–Aβ interaction, by which resulting in the neurotoxicity of Aβ and free radical damage. Here, we employed a mutant Aβ (Aβ H13R) in which a histidine residue was replaced by arginine. Copper facilitated the precipitation of both wild-type and mutant Aβ in the spectrophotometric absorbance assay but suppressed β-structure aggregates according to Thioflavine-T assay. Wild-type Aβ alone is more cytotoxic but produced less amount of H2O2 than AβH13R–copper complexes, suggesting that Aβ–membrane interaction may also implicated in the pathologic progress. Aβ toxicity is in positive correlation to its competence to aggregate despite the aggregation is mainly composed of non-β fibril substances. In short, these findings may provide further evidence on the role of copper in the pathogenesis of Alzheimer’s disease.

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Abbreviations

AD:

Alzheimer’s disease

Aβ:

amyloid-β peptide

APP:

amyloid precursor protein

SPs:

senile plaques

NFTs:

neurofibrillary tangles

CD:

circular dichroism

HFIP:

1,1,1,3,3,3-hexafluoro-2-propanol

ThT:

Thioflavine-T

DMEM:

Dulbecco’s modified Eagle’s medium

OD:

optical density

MTT:

3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

DMSO:

dimethyl sulfoxide

LDH:

lactate dehydrogenase

13Aβ40:

Aβ(1–40)H13R

WT Aβ40 :

wild-type Aβ (1–40)

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Acknowledgment

This work was supported by grants from the Key Program of the Beijing Natural Science Foundation (Project No: KZ200311417015) and the Funding Project for Academic Human Resources Development in Institutions of Higher Learning Under the Jurisdiction of Beijing Municipality, PHR(IHLB) [PHR20090513].

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Authors and Affiliations

  1. Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing, 100191, China

    Xueling Dai & Zhaofeng Jiang

  2. Department of Biology, College of Applied Sciences and Humanities, Beijing Union University, Beijing, 100191, China

    Xueling Dai, Yaxuan Sun, Zhaolan Gao & Zhaofeng Jiang

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  1. Xueling Dai
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  2. Yaxuan Sun
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  3. Zhaolan Gao
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  4. Zhaofeng Jiang
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Correspondence to Zhaofeng Jiang.

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Dai, X., Sun, Y., Gao, Z. et al. Copper Enhances Amyloid-β Peptide Neurotoxicity and non β-Aggregation: A Series of Experiments Conducted upon Copper-Bound and Copper-Free Amyloid-β Peptide. J Mol Neurosci 41, 66–73 (2010). https://doi.org/10.1007/s12031-009-9282-8

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  • DOI: https://doi.org/10.1007/s12031-009-9282-8

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