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

The aggregation of beta-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 A beta-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, A beta(16-22), and its parent peptide, A beta(1-42). 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 A beta(16-22) and A(beta 1-42) from beta to non-beta 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 A beta(1-42) in human cerebrospinal fluid to verify EF-mediated modulation. The self-seeding of Afi,_42 and cross-seeding with A beta(1-40) 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. A beta-elicited toxicity of EF-treated samples in two neuroblastoma cell lines (SH-SYSY 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 A beta(1-42) 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.