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

William P. Esler, Evelyn R. Stimson, Joan M. Jennings, Joseph R. Ghilardi, Patrick W Mantyh, John E. Maggio

Research output: Contribution to journalArticle

114 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)723-732
Number of pages10
JournalJournal of Neurochemistry
Volume66
Issue number2
StatePublished - Feb 1996
Externally publishedYes

Fingerprint

Amyloid
Zinc
Rats
Agglomeration
Peptides
Alzheimer Disease
Amyloid Plaques
Centrifugation
Immunoassay
Plastics
Cations
Proteins
Salts
Metals
Density (optical)
Amino Acids
In Vitro Techniques
Brain
Tissue

Keywords

  • β-Amyloid
  • Aggregation
  • Alzheimer's disease
  • Zinc

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Esler, W. P., Stimson, E. R., Jennings, J. M., Ghilardi, J. R., Mantyh, P. W., & Maggio, J. E. (1996). Zinc-induced aggregation of human and rat β-amyloid peptides in vitro. Journal of Neurochemistry, 66(2), 723-732.

Zinc-induced aggregation of human and rat β-amyloid peptides in vitro. / Esler, William P.; Stimson, Evelyn R.; Jennings, Joan M.; Ghilardi, Joseph R.; Mantyh, Patrick W; Maggio, John E.

In: Journal of Neurochemistry, Vol. 66, No. 2, 02.1996, p. 723-732.

Research output: Contribution to journalArticle

Esler, WP, Stimson, ER, Jennings, JM, Ghilardi, JR, Mantyh, PW & Maggio, JE 1996, 'Zinc-induced aggregation of human and rat β-amyloid peptides in vitro', Journal of Neurochemistry, vol. 66, no. 2, pp. 723-732.
Esler WP, Stimson ER, Jennings JM, Ghilardi JR, Mantyh PW, Maggio JE. Zinc-induced aggregation of human and rat β-amyloid peptides in vitro. Journal of Neurochemistry. 1996 Feb;66(2):723-732.
Esler, William P. ; Stimson, Evelyn R. ; Jennings, Joan M. ; Ghilardi, Joseph R. ; Mantyh, Patrick W ; Maggio, John E. / Zinc-induced aggregation of human and rat β-amyloid peptides in vitro. In: Journal of Neurochemistry. 1996 ; Vol. 66, No. 2. pp. 723-732.
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