Oligomeric Amyloid-β Toxicity Can Be Inhibited by Blocking Its Cellular Binding in Cortical Neuronal Cultures with Addition of the Triphenylmethane Dye Brilliant Blue G

Accumulation of soluble amyloid beta (A beta) oligomers in the brain has been suggested to cause neurodegeneration associated with Alzheimer's disease (AD). Our previous findings showed that the binding of A beta trimer and tetramer to neurons is significantly correlated with A beta-induced neuronal cell death. We propose blocking of neuronal binding of these neurotoxic A beta oligomers as a therapeutic strategy for preventing this disease. To test this, a nontoxic triphenylmethane dye, Brilliant Blue G (BBG), which has been reported to modulate A beta aggregation and neurotoxicity, was investigated using mouse primary cortical neuronal cultures treated with photoinduced cross-linked toxic A beta 40 oligomers as well as soluble A beta 40 and A beta 42 peptides. We found that the BBG-induced decrease in A beta binding resulted in a significant decrease in its neurotoxicity. These findings support our hypothesis that disruption of cellular A beta binding is a promising therapeutic strategy for combating AD.