Interaction of synthetic Alzheimer beta-protein-derived analogs with aqueous aluminum: A low-field Al-27 NMR investigation

1Synthetic peptides corresponding to the soluble Alzheimer beta-protein, i.e., beta 1-40 and beta 6-25, were utilized to investigate the association of aluminum using low-field Al-27 nuclear magnetic resonance (NMR) spectroscopy and reversed-phase high-performance liquid chromatography (RP-HPLC). Addition of beta 1-40 or beta 6-25 to aqueous Al3+ gives rise to a Al-27 NMR signal corresponding to the association of Al3+ with the peptides; this effect is not easily reversed by EDTA. Based on the relative intensity of the Al3+-peptide signal between pH 4 and 6, there are at least 4 Al3+ ions associated with each peptide molecule. Microheterogeneity is observed with RP-HPLC on incubating solutions of Al3+ with beta 1-40 and beta 6-25. The Al-27 NMR spectra of chromatographically pure fractions of beta 1-40 and beta 6-25 indicate that the peptide-associated Al3+ is released below pH 3.5. We propose that soluble beta 1-40 provides an anchor for Al3+ to bind, eventually leading to an increased deposition of amyloid in the Alzheimer brain.