Alzheimer's disease is a lethal neurodegenerative pathology accompanied by the formation of water-soluble neurotoxic oligomers of the human β-amyloid peptide, Aβ, which are then accumulated as polymeric extracellular aggregates (the so-called amyloid plaques). The human Aβ isoform isomerized at aspartate 7 (isoAβ) is the major component of amyloid plaques and is regarded as a potential causative agent for Alzheimer's disease. A mechanism for producing this isoform from a genetically determined variant of D7N β-amyloid (Tottori mutation) has been proposed. However, the rat/mouse Aβ (ratAβ), which carries three amino acid substitutions in metal-binding domain 1-16, is not susceptible to pathogenic aggregation in vivo, unlike the other known genetically determined or chemically modified natural Aβ isoforms. The nteractions with zinc ion play a key role in the in vitro and in vivo aggregation of monomeric human Aβ. Here, we have used high-resolution ESI-MS to demonstrate for the first time that domains 1-16 of the isoforms isoAβ and D7N-Aβ bind zinc ion in exactly the same manner as human 1-16 Aβ domain. On the other hand, the structure of the minimal zinc-binding center in ratAβ differs significantly. These results confirm the general mechanism underlying the interaction of zinc ions with human Aβ isoforms and suggest that structural modulations of Aβ region 6-14 can be used as a promising approach to the therapy of Alzheimer's disease.