A boundary dance of amyloid-beta stepping into dementia

The research group at Exploratory Research Center on Life and Living Systems and Institute for Molecular Science, Japan worked on this problem using molecular dynamics simulations and nuclear magnetic resonance spectroscopy experiments. They found that the Aβ peptides tend to gather at the hydrophilic/hydrophobic interface. That is, the local concentration of Aβ at the interface is higher than that in bulk water solution. In addition, β-hairpin structures are formed more at the interface than in the bulk water solution. In the β-hairpin structure, as shown in the figure, a part of the Aβ peptide extends straight and forms intramolecular hydrogen bonds. Therefore, another Aβ peptide that comes close to this peptide is easy to make intermolecular hydrogen bonds and tends to aggregate. In this way, the research group clarified that the reason for accelerating the aggregation of the Aβ peptides on the cell membrane surface is that not only the Aβ peptide tends to have high concentration on the cell membrane surface but also it takes a structure that tends to bind to each other.

This discovery enables us to elucidate the mechanism by which the Aβ peptide aggregates on the membrane surface of nerve cells. Elucidating this mechanism will be applied to developing inhibitors against the causative substances of Alzheimer's disease in the future.