Amyloid- peptide (142) aggregation induced by copper ions under acidic conditions

It is well known that the aggregation of amyloid- peptide (A) induced by Cu-2 is related to incubation time, solution pH, and temperature. In this work, the aggregation of A(142) in the presence of Cu-2 under acidic conditions was studied at different incubation time and temperature (e.g. 25 and 37C). Incubation temperature, pH, and the presence of Cu-2 in A solution were confirmed to alter the morphology of aggregation (fibrils or amorphous aggregates), and the morphology is pivotal for A neurotoxicity and Alzheimer disease (AD) development. The results of atomic force microscopy (AFM) indicated that the formation of A fibrous morphology is preferred at lower pH, but Cu-2 induced the formation of amorphous aggregates. The aggregation rate of A was increased with the elevation of temperature. These results were further confirmed by fluorescence spectroscopy and circular dichroism spectroscopy and it was found that the formation of -sheet structure was inhibited by Cu-2 binding to A. The result was consistent with AFM observation and the fibrillation process was restrained. We believe that the local charge state in hydrophilic domain of A may play a dominant role in the aggregate morphology due to the strong steric hindrance. This research will be valuable for understanding of A toxicity in AD.