Redox-active iron mediates amyloid-β toxicity

Catherine Rottkamp, Arun K. Raina, Xiongwei Zhu, Elizabeth Gaier, Ashley I. Bush, Craig S. Atwood, Mordechai Chevion, George Perry, Mark A. Smith

Research output: Contribution to journalArticlepeer-review

336 Scopus citations


While amyloid-β toxicity is mediated by oxidative stress and can be attenuated by antioxidants, the actual biochemical mechanism underlying neurotoxicity remains to be established. However, since aggregated amyloid-β can interact with transition metals, such as iron, both in vitro and in vivo, we suspected that bound iron might be the mediator of toxicity such that holo- and apo-amyloid would have differential effects on cellular viability. Here we demonstrate that when amyloid-β is pretreated with the iron chelator deferoxamine, neuronal toxicity is significantly attenuated while conversely, incubation of holo-amyloid-β with excess free iron restores toxicity to original levels. These data, taken together with the known sequelae of amyloid-β, suggest that the toxicity of amyloid-β is mediated, at least in part, via redox-active iron that precipitates lipid peroxidation and cellular oxidative stress.

Original languageEnglish (US)
Pages (from-to)447-450
Number of pages4
JournalFree Radical Biology and Medicine
Issue number4
StatePublished - Feb 15 2001
Externally publishedYes


  • Alzheimer disease
  • Amyloid-β
  • Free radicals
  • Iron
  • Neurotoxicity
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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