Abstract
The major pathological feature of Alzheimer's disease is the presence of a high density of amyloid plaques in the brain tissue of patients. The plaques are predominantly composed of human β-amyloid peptide (Aβ), a 39-43-mer peptide the neurotoxicity of which is related to its aggregation state. Previous work has demonstrated that certain metals that have been implicated as risk factors for Alzheimer's disease (Al, Fe, and Zn) also cause substantial aggregation of Aβ. In particular, we reported that zinc cations at concentrations of >10-4 M dramatically accelerate the rate of Aβ aggregation at physiological peptide concentrations at 37°C in vitro. In the present study, we investigate the effect of Zn2+ on aggregation of radiolabeled and unlabeled human and rat Aβ over a wide range of peptide concentrations in the presence and absence of salt and blocking protein. Aggregation was assayed by centrifugation and filtration using amino acid analysis, immunoassay, and γ-counting for quantification over a wide range of concentrations of Zn2+ and Aβ above and below physiological values. The results of this study demonstrate the following: (a) Radioiodinated Aβ accurately tracked unlabeled Aβ, (b) zinc concentrations of at least 10-4 M were required to induce significant aggregation of Aβ, and (c) rat and human Aβ species were cleared from aqueous solutions by similar concentrations of zinc. These results stand in significant quantitative disagreement (~100-fold in zinc concentration) with one previous study that reported significant aggregation of Aβ by <1 μM Zn2+. Differences between the present study and the latter study from another laboratory appear to result from inappropriate reliance on optical density to measure Aβ concentrations and nonspecific loss of Aβ to plastic in the absence of blocking protein.
Original language | English (US) |
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Pages (from-to) | 723-732 |
Number of pages | 10 |
Journal | Journal of neurochemistry |
Volume | 66 |
Issue number | 2 |
DOIs | |
State | Published - Feb 1996 |
Keywords
- Aggregation
- Alzheimer's disease
- Zinc
- β-Amyloid
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience