Origins of the Superiority of Oscillating Electric Fields for Disrupting Senile Plaques: Insights from the 7-Residue Fragment and the Full-length Aβ-42 Peptide.

Our recent molecular dynamics simulations of decomposing Alzheimer's disease plaques, under oscillating- and static external electric fields (Os-EEFs and St-EEFs), revealed the superiority of Os-EEF for decomposing plaques consisting of the 7-residue peptide segment. This conclusion is now reinforced by studying the dimers of the short peptides and trimers of the full-length Aβ-42 peptide. Thus, the dispersed peptides obtained following St-EEF applications reformed the plaques once the St-EEF subsided. In contrast, . The present study provides insights into these results by modeling the decomposition modes that transpire under both field types. Additionally, this study provides insights into the frequency effects on the decomposition processes within the THz-MHz regions. The simulation shows that the Os-EEF in the lower frequency range (≤GHz) decomposes the plaque on a time scale of ∼50 ns, whereas the higher frequency Os-EEFs (≥THz) are less effective. As such, Os-EEFs with moderate-to-low frequencies (≤GHz) lead to an "explosion," whereby the peptides fly distantly apart and inhibit plaque reformation. By contrast, St-EEFs form parallel peptide pairs, which are stabilized by the EEF due to the large dipole moment of the ensemble. Thus, St-EEF applications lead to sluggish and reversible plaque decomposition processes. We further conclude that the Os-EEF impact is maximal for short pulses, which prevents the EEF propensity to arrange the peptides in parallel pairs. The superiority of the Os-EEF over the St-EEF is maintained irrespective of the peptides' length. A model is formulated that predicts the dependence of the decomposition time scale on the EEF.