Impact of ultrafine particles and secondary inorganic ions on early onset and progression of amyloid aggregation: Insights from molecular simulations

Alzheimer's disease (AD) is a neurodegenerative disorder, associated with the aggregation of amyloid beta (AP) peptides and formation of plaques. The impact of airborne particulate matter (PM) and ultrafine particles (UFPs), on early onset and progression of AD has been recently hypothesized. Considering their small size, carbon black nanoparticles and UFPs can penetrate into human organism and affect Alzheimer's progression. While experiments show that the exposure of PM and UFPs can lead to enhanced concentrations of A beta peptides, the interactions between the peptides and UFPs remain obscured. Particularly, the impact of UFPs on the initial rate of aggregation of the peptides is ambiguous. Herein, we perform molecular dynamics simulations to investigate the aggregation of A beta(16)(-)(21) peptides, an aggregation-prone segment of Al3, in the presence of UFPs, mimicked by C-60, under different salt solutions suggesting the presence of the inorganic constituents of PM in the blood. In particular, the simulations were performed in the presence of Na+, Cl- and CO(3)(2- )ions to characterize typical buffer environments and electrolytes present in human blood. Furthermore, NH4+, NO3- and SO4-2 ions, found in PM, were used in the simulations. The results revealed high propensity for the aggregation of A beta(16-21) peptides. Moreover, the peptides made clusters with C(60)molecules, that would be expected to act as a nucleation site for the formation of amyloid plaques. Taken together, the results showed that UFPs affected the peptide aggregation differently, depending on the type of ions present in the simulation environment. In the presence of C-60, SO4-2 and NO3- ions accelerated the aggregation of A beta(16)(-)(21)peptides, however, NH4+ ions decelerated their aggregation. In addition, UFP lowered beta-sheets amounts at all environments, except NaCl solution. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

It is hypothesized that airborne particulate matter and ultrafine particles can influence the early onset and progression of Alzheimer's disease by impacting the aggregation of amyloid beta peptides. Molecular dynamics simulations revealed that ultrafine particles affected the aggregation of Aβ(16-21) peptides differently based on the type of ions present in the simulation environment. The presence of certain ions such as SO4-2 and NO3- accelerated the aggregation of Aβ(16-21) peptides in the presence of C-60, while NH4+ ions decelerated their aggregation.