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 (Aβ) 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 Aβ 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 Aβ_16-21 peptides, an aggregation-prone segment of Aβ, in the presence of UFPs, mimicked by C₆₀, 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 CO₃⁻² 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 Aβ_16-21 peptides. Moreover, the peptides made clusters with C₆₀ 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 C₆₀, SO₄⁻² and NO₃⁻ ions accelerated the aggregation of Aβ_16-21 peptides, however, NH₄⁺ ions decelerated their aggregation. In addition, UFP lowered β-sheets amounts at all environments, except NaCl solution.