Iron and Aluminum Interaction with Amyloid-beta Peptides Associated with Alzheimer's Disease

摘要

An elevation in the concentration of heavy metal ions in Alzheimer's disease (AD) brain has been demonstrated in many studies. Aβ precipitation and toxicity in AD brains seem to be caused by abnormal interactions with neocortical metal ions, especially iron, copper, zinc, and aluminum. There is increasing evidence that iron and aluminum ions are involved in the mechanisms that underlie the neurodegenerative diseases. However, evidence was brought to demonstrate that some Aβ fragments, at physiological pH, are not able to form binary complexes with Fe(Ⅲ) ions of sufficient stability to compete with metal hydroxide precipitation. On the contrary, multiple metal ions are known to interact with Ap peptides. Consequently, we investigated here the interaction of Fe(Ⅱ/Ⅲ) and Al(Ⅲ) ions with some amyloid-P peptides and fragments that results in peptide aggregation and fibrillation. Infrared spectroscopy, atomic force microscopy, scanning electron microscopy, electrophoresis and mass spectrometry demonstrated conformational changes of peptides in the presence of such metals.