Metals and Neuronal Metal Binding Proteins Implicated in Alzheimer’s Disease

Figure 1

Modulation of amyloid-β aggregation by Cu²⁺ and Zn²⁺ binding. Aβ aggregation into fibrils is a complex pathway that involves multiple intermediate precursor species. The scheme is a simplification depicting direct effects of Cu²⁺ and Zn²⁺ on Aβ aggregation. Superstoichiometric levels of Cu²⁺ and Zn²⁺ (Zn²⁺/Cu²⁺: ) result in insoluble and amorphous aggregates rather than organized fibrils, while equimolar Cu²⁺ and Zn²⁺ (Zn²⁺/Cu²⁺: ) induce amorphous aggregates, which slowly convert to fibrils. At subequimolar Cu²⁺ levels (Cu²⁺: ), the kinetics of fibril formation are accelerated. The AD amyloid plaques, depicted in a representation at the bottom right corner of the figure, contain high levels of Zn (1055 μM), Fe (940 μM), and Cu (390 μM), as reviewed in [35]. See text for details.