The Aggregation Pattern of Aβ1-40 is Altered by the Presence of N-Truncated Aβ4-40 and/or CuII in a Similar Way through Ionic Interactions

Alzheimer's disease (AD) is one of the most common of the multifactorial diseases and is characterized by a range of abnormal molecular processes, such as the accumulation of extracellular plaques containing the amyloid-beta (A beta) peptides and dyshomeostasis of copper in the brain. In this study, we have investigated the effect of Cu-II on the aggregation of A beta(1-40) and A beta(4-40), representing the two most prevalent families of A beta peptides, that is, the full length and N-truncated peptides. Both families are similarly abundant in healthy and AD brains. For either of the studied peptides, substoichiometric Cu-II concentrations accelerated aggregation, whereas superstoichiometric Cu-II inhibited fibril formation, likely by stabilizing the oligomers. The addition of either A beta(4-40) or substoichiometric Cu-II affected the aggregation profile of A beta(1-40), by yielding shorter and thicker fibrils; amorphous aggregates were formed in the presence of a molar excess of Cu-II. The similarity of these two effects can be attributed to the increase in the positive charge on the A beta N terminus, caused both by Cu-II complexation and N truncation at position 4. Our findings provide a better understanding of the biological A beta aggregation process as these two A beta species and Cu-II coexist and interact under physiological conditions.

Automated summary

This study investigated the effect of Cu-II on the aggregation of A beta(1-40) and A beta(4-40). It was found that substoichiometric Cu-II concentrations accelerated aggregation, while superstoichiometric Cu-II inhibited fibril formation. The interaction between Cu-II, A beta(4-40), and A beta(1-40) resulted in significant changes in the aggregation process.