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. 2006 Apr 5;14(4):448–452. doi: 10.1111/j.1750-3639.2004.tb00089.x

The Amyloid Paradox: Amyloid‐β‐Metal Complexes can be Neurotoxic and Neuroprotective

Glenda M Bishop 1,✉, Stephen R Robinson 1
PMCID: PMC8095825  PMID: 15605992

Abstract

Senile plaques in the brains of people with Alzheimer disease (AD) are primarily composed of the amyloid‐β (Aβ) peptide and contain substantially elevated levels of iron, copper and zinc. These metals bind to Aβ and have been reported to increase the toxicity of Aβ to cultured neurones. Other reports have demonstrated that Aβ can reduce the neurotoxicity of metal ions, suggesting that the interaction can, under some circumstances, be protective. To investigate these apparently conflicting results, human Aβi‐42 was co‐injected with iron, copper or zinc (at the concentrations found in plaques) into rat cerebral cortex, and the resulting numbers of dying neurones were compared. It was found that Aβ complexed with either iron or zinc was more toxic than Aβ alone. In contrast, Aβ‐copper complexes were not neurotoxic. Surprisingly, we observed that when iron or copper were combined with Aβ, the neurotoxicity of these metals was substantially reduced, suggesting that Aβ may help to limit the toxicity of redox‐active metal ions, thereby assisting the antioxidant defence of the brain. Thus paradoxical effects occur when AP complexes with metal ions, where Aβ‐metal complexes are capable of being neurotoxic and neuroprotective.

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