A hallmark of Alzheimer's disease is the accumulation of insoluble fibrils in the brain composed of amyloid beta (Aβ) proteins with parallel in-register cross-β-sheet structure. It has been suggested that the aggregation of monomeric Aβs into fibrils is promoted by “seeds” that form within compartments of the brain that have limited solvent due to macromolecular crowding. In our previous report, a crowded macromolecular environment was mimicked by encapsulating monomers of Aβs into reverse micelles (RMs), formed from AOT, sodium bis(2-ethylhexyl) sulfosuccinate. We demonstrated that the crowded environment of the RMs induced the formation of β-strand seed structures for nucleating amyloid fibril formation.1 Copper is a redox-active metal with many important biological roles, and the dysregulation of copper is intimately involved in the pathogenesis of Alzheimer's disease. In the present study, we have encapsulated a short 1-16 residue form of the Aβs as well as the 40- and 42-residues forms into RMs and examined them in the presence of copper ion with transmission Fourier-transform infrared spectroscopy. We propose a mechanism for the effect of copper ion on the formation of amyloid fibril seeds, involving the formation of a coordination complex with the His residues at position 13 and 14 on a pair of Aβ molecules and inducing in-register alignment of the N-terminal residues. Ref. (1) Yeung, P. S.-W., and Axelsen, P. H. (2012) J. Am. Chem. Soc., 134, 6061-6063.