Effect of Ca2+ on Aß40 fibrillation is characteristically different

• Previously, we reported enhanced acceleration of Aβ42 fibril formation by Ca2+ as compared to Aβ40 (in vitro).
• We used different but scientific data treatment and parameters in this study.
• We conclude, although subtle and elusive, Ca2+ at physiological concentrations and in vitro enhances Aβ40 fibrillation at monomeric, oligomeric and protofibrilar stages contrary to published reports but it is not as prominent as observed for Aβ42.

Alzheimer’s disease (AD) is the only one among top ten diseases in USA that cannot be cured, prevented or slowed down. At molecular level the mechanism of onset has been closely associated with mis-folding of Aβ40 and Aβ42 and is well supported by the genetic data for AD. Extensive research efforts have led to identification of factors and metal ions that could manipulate Aβ equilibrium, especially Ca2+. Previously, we reported selectively acceleration of Aβ42 fibril formation by Ca2+in vitro within physiological concentrations (BBA (2009) 1794:1536). Aβ40 on the other hand did not appear to be significantly affected by Ca2+ addition. In an effort to understand the distinctive behavior of Aβ40, we monitored changes of Aβ40 aggregation by intrinsic tyrosine fluorescence and CD and took different approaches for data processing. Our analysis of CD data indicates a complex effect induced by the addition of 2 mM Ca2+ resulting in an increase in the rate of transformation from monomer to β-sheet rich fibrilar or intermediate species formation in Aβ40. Surprisingly, the kinetics observed by intrinsic fluorescence studies in this article and ThT, SEC or EM studies in our previous report were not able to unravel the existence of this effect in Aβ40.