Dramatic aggregation of alzheimer by Cu(II) is induced by conditions representing physiological acidosis

Abstract

The cortical deposition of Aβ is an event that occurs in Alzheimer's disease, Down's syndrome, head injury, and normal aging. Previously, in appraising the effects of different neurochemical factors that impact upon the solubility of Aβ, we observed that Zn2+ was the predominant bioessential metal to induce the aggregation of soluble Aβ at pH 7.4 in vitro and that this reaction is totally reversible with chelation. We now report that unlike other biometals tested at maximal biological concentrations, marked Cu2+-induced aggregation of Aβ1-40 emerged as the solution pH was lowered from 7.4 to 6.8 and that the reaction was completely reversible with either chelation or alkalinization. This int..