Disrupting Dimeric β-Amyloid by Electric Fields.

Area of Science:

• Biophysics
• Neuroscience
• Computational Chemistry

Background:

• Early oligomers of amyloid beta (Aβ) peptides are linked to Alzheimer's disease pathogenesis.
• The transient nature of these Aβ oligomers hinders structural characterization and understanding of their toxicity.
• Minimal toxic species, such as β-amyloid dimers, are key targets for therapeutic intervention.

Purpose of the Study:

• To investigate the structural stability of Aβ42 dimers under oscillating electric fields.
• To explore the potential of electric fields in disrupting toxic amyloid oligomers.

Main Methods:

• Utilized deep learning (AlphaFold-multimer) to generate initial models of Aβ42 dimers.
• Employed molecular dynamics (MD) simulations to analyze dimer flexibility and secondary structure.
• Conducted MD simulations with an external oscillating electric field (1 GHz) to assess stability.

Main Results:

• Structurally stable Aβ42 dimer models were identified, consistent with microsecond-long MD sampling.
• High-strength oscillating electric fields induced a rapid decay of β-sheet content in Aβ42 dimers.
• Aβ42 dimers exhibited lower structural stability compared to helical leucine zipper peptide dimers under electric fields.

Conclusions:

• External oscillating electric fields can disrupt the structure of amyloid oligomers.
• This finding suggests a potential novel approach for targeting Alzheimer's disease pathology.
• Further experimental validation using brain organoids and in vivo studies is warranted.