PMID: 8592145Feb 1, 1996Paper

Zinc-induced aggregation of human and rat beta-amyloid peptides in vitro

Journal of Neurochemistry
W P EslerJ E Maggio

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 beta-amyloid peptide (A beta), 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 A beta. In particular, we reported that zinc cations at concentrations of > 10(-4) M dramatically accelerate the rate of A beta aggregation at physiological peptide concentrations at 37 degrees C in vitro. In the present study, we investigate the effect of Zn2+ on aggregation of radiolabeled and unlabeled human and rat A beta 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 gamma-counting for quantification over a wide range of concentrations of Zn2+ and A beta above and below physiological values. The results of this study demonstrate the following: (a) Radioiodinated A beta accurately tracked unlabeled A beta...Continue Reading

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