Therapeutics for Alzheimer's Disease Based on the Metal Hypothesis

Abstract

Alzheimer's disease is the most common form of dementia in the elderly, and it is characterized by elevated brain iron levels and accumulation of copper and zinc in cerebral β-amyloid deposits (e.g., senile plaques). Both ionic zinc and copper are able to accelerate the aggregation of Aβ, the principle component of β-amyloid deposits. Copper (and iron) can also promote the neurotoxic redox activity of Aβ and induce oxidative cross-linking of the peptide into stable oligomers. Recent reports have documented the release of Aβ together with ionic zinc and copper in cortical glutamatergic synapses after excitation. This, in turn, leads to the formation of Aβ oligomers, which, in turn, modulates ..