The Cu(II)/Aβ/Human Serum Albumin Model of Control Mechanism for Copper-Related Amyloid Neurotoxicity

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the elderly population, above 65 years of age. Multiple lines of evidence confirm the central role of 40−42 residue Aβ peptides in the pathogenesis of AD, but exact mechanisms of Aβ toxicity remain unclear. Recently, evidence has accumulated in favor of small oligomers of the Aβ42 peptide as major toxic species. Metal ions, copper(II) in particular, have been implicated in molecular mechanisms of Aβ neurotoxicity, including oxidative damage of lipid membranes. While monomeric Aβ peptides are not neurotoxic, the deep understanding of their chemical properties is prerequisite for significant progress in Alzheimer research. Monomeric Aβ40 and Aβ42 form a specific mononuclear complex with Cu(II), recruiting donor atoms within their common 16 amino acid N-terminal sequence. The formation of this complex, the exact structure of which is debated, correlates with increased Aβ toxicity. Human serum albumin (HSA) is a versatile carrier protei...