Phenolic Compounds Prevent Amyloid β-Protein Oligomerization and Synaptic Dysfunction by Site-specific Binding

Cerebral deposition of amyloid beta protein (A beta) is an invariant feature of Alzheimer disease (AD), and epidemiological evidence suggests that moderate consumption of foods enriched with phenolic compounds reduce the incidence of AD. We reported previously that the phenolic compounds myricetin (Myr) and rosmarinic acid (RA) inhibited A beta aggregation in vitro and in vivo. To elucidate a mechanistic basis for these results, we analyzed the effects of five phenolic compounds in the A beta aggregation process and in oligomer-induced synaptic toxicities. We now report that the phenolic compounds blocked A beta oligomerization, and Myr promoted significant NMR chemical shift changes of monomeric A beta. Both Myr and RA reduced cellular toxicity and synaptic dysfunction of the A beta oligomers. These results suggest that Myr and RA may play key roles in blocking the toxicity and early assembly processes associated with A beta through different binding.