Zinc-induced Alzheimer's Aβ1-40 aggregation is mediated by conformational factors

Abstract

The heterogeneous precipitates of Aβ that accumulate in the brain cortex in Alzheimer's disease possess varying degrees of resistance to resolubilization. We previously found that Aβ1-40 is rapidly precipitated in vitro by physiological concentrations of zinc, a neurochemical that is highly abundant in brain compartments where Aβ is most likely to precipitate. We now present evidence that the zinc-induced precipitation of Aβ is mediated by a peptide dimer and favored by conditions that promote α-helical and diminish β-sheet conformations. The manner in which the synthetic peptide is solubilized was critical to its behavior in vitro. Zinc-induced Aβ aggregation was dependent upon the presence..