Metal-catalyzed oxidative damage and oligomerization of the amyloid-peptide of Alzheimer's disease

The most common form of dementia in old age is Alzheimer's disease ( AD). The presence in the brain of senile plaque is the major pathological marker of AD. The plaques are primarily composed of aggregated amyloid-beta peptide (Abeta). Abeta is a 40 - 42 amino acid peptide that is a proteolytic product derived from the beta-amyloid precursor protein. The function of Abeta and the exact mechanism of Abeta aggregation and neurotoxicity are unclear. However, metal coordination by Abeta plays an important role in inducing aggregation and the generation of reactive oxygen species, which appears to be at least partially responsible for Abeta neurotoxicity. In this review we examine the role of copper and zinc ions in Abeta neurotoxicity, especially with regards to the generation of free radicals. We discuss the role of copper or zinc ions in oxidative damage and Abeta conformational changes and the relationship of these metals to AD.