Local structure and global patterning of Cu2+ binding in fibrillar amyloid-β [Aβ(1-40)] protein.

The amyloid-β (Aβ) protein forms fibrils and higher-order plaque aggegrates in Alzheimer's disease (AD) brain. The copper ion, Cu(2+), is found at high concentrations in plaques, but its role in AD etiology is unclear. We use high-resolution pulsed electron paramagnetic resonance spectroscopy to characterize the coordination structure of Cu(2+) in the fibrillar form of full-length Aβ(1-40).

Cu(II) binding to monomeric, oligomeric, and fibrillar forms of the Alzheimer's disease amyloid-beta peptide.

Copper has been proposed to play a role in Alzheimer's disease through interactions with the amyoid-beta (Abeta) peptide. The coordination environment of bound copper as a function of Cu:Abeta stoichiometry and Abeta oligomerization state are particularly contentious. Using low-temperature electron paramagnetic resonance (EPR) spectroscopy, we spectroscopically distinguish two Cu(II) binding sites on both soluble and fibrillar Abeta (for site 1, A parallel = 168 +/- 1 G and g parallel = 2.

N-Terminal deletions modify the Cu2+ binding site in amyloid-beta.

Copper is implicated in the in vitro formation and toxicity of Alzheimer's disease amyloid plaques containing the beta-amyloid (Abeta) peptide (Bush, A. I., et al.

Amyloid-beta binds Cu2+ in a mononuclear metal ion binding site.

Amyloid-beta (Abeta) peptide is the principal constituent of plaques associated with Alzheimer's disease and is thought to be responsible for the neurotoxicity associated with the disease. Metal ions have been hypothesized to play a role in the formation and neurotoxicity of aggregates associated with Alzheimer's disease (Bush, A. I.