Monitoring the early aggregatory behaviour and size of Aβ1-42 in the absence & presence of metal ions using dynamic light scattering

Background and aim: A beta(1-42) is an amyloidogenic peptide found within senile plaques extracted from those who died with a diagnosis of Alzheimer's disease. The potent neurotoxicity of this peptide is related to its propensity to form aggregated conformations in vivo, a process that is influenced by the species and concentration of metal ions present within the local environment. This study examines the impact of different metals upon the early aggregatory behaviour and size of A beta(1-42) under simulated physiological conditions.Methods: The size and aggregatory behaviour of A beta(1-42) in the presence and absence of metal ions was monitored during the initial 30 min of fibril formation in real-time using dynamic light scattering.Results: Intensity scattering measurements showed a clear tendency towards aggregation with regards to A beta(1-42) only solutions (10 mu M). Both equimolar Al3+ & Cu2+ lowered and stabilised the dimensions of A beta(1-42) aggregates; however, a diminutive but significant increase in size was still observed over a 30-min period. While excess Al3+ continued to supress the size of A beta(1-42), a 10-fold increase in the concentration of Cu2+ accelerated peptide aggregation relative to that observed for equimolar metal but not compared to A beta(1-42) alone.Conclusion: These results infer that Al3+ ions stabilise and aid in the maintenance of smaller, toxic intermediates while excess Cu2+ facilitates the formation of larger, more inert, amorphous species exceeding 1 mu m in size. Furthermore, we propose that metal-induced toxicity of A beta(1-42)