Electric Field Disruption of Amyloid Aggregation: Potential Noninvasive Therapy for Alzheimer's Disease.

Abstract

The aggregation of β-amyloid peptides is a key event in the formative stages of Alzheimer's disease. Promoting folding and inhibiting aggregation was reported as an effective strategy in reducing Aβ-elicited toxicity. This study experimentally investigates the influence of the external electric field (EF) and magnetic field (MF) of varying strengths on the in vitro fibrillogenesis of hydrophobic core sequence, Aβ16-22, and its parent peptide, Aβ1-42. Biophysical methods such as ThT fluorescence, static light scattering, circular dichroism, and infrared spectroscopy suggest that EF has a stabilizing effect on the secondary structure, initiating a conformational switch of Aβ16-22 and Aβ1-42 from β to non-β conformation. This observation was further corroborated by dynamic light scattering and transmission electron microscopic studies. To mimic in vivo conditions, we repeated ThT fluorescence assay with Aβ1-42 in human cerebrospinal fluid to verify EF-mediated modulation. The self-seeding of Aβ1-42 and cross-seeding with Aβ1-40 to verify that the autocatalytic amplification of self-assembly as a result of secondary nucleation also yields comparable results in EF-exposed and unexposed samples. Aβ-elicited toxicity of EF-treated samples in two neuroblastoma cell lines (SH-SY5Y and IMR-32) and human embryonic kidney cell line (HEK293) were found to be 15-38% less toxic than the EF untreated ones under identical conditions. Experiments with fluorescent labeled Aβ1-42 to correlate reduced cytotoxicity and cell internalization suggest a comparatively smaller uptake of the EF-treated peptides. Our results provide a scientific roadmap for future noninvasive, therapeutic solutions for the treatment of Alzheimer's disease.