Inhibition of Amyloid β-Induced Lipid Membrane Permeation and Amyloid β Aggregation by K162

Alzheimer’s disease (AD) is characterized by progressive neurodegeneration associated with amyloid β (Aβ) peptide aggregation. The aggregation of Aβ monomers (AβMs) leads to the formation oligomers (AβOs), neurotoxic form, capable permeating cell membrane. Here, we investigated effect a fluorene-based active drug candidate, named K162, on both and AβO toxicity toward bilayer lipid membrane (BLM). Electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM), molecular dynamics (MD) were employed show that K162 inhibits AβOs-induced BLM permeation, thus preserving integrity. In presence only shallow defects surface formed. Apparently, modifies bypassing toxic AβOs, nontoxic AβMs, dimers (AβDs), fibrils (AβFs) are produced. Unlike other inhibitors, preserves neurologically beneficial AβMs. This unique inhibition mechanism provides an alternative AD therapeutic strategy could be explored in future.