In this study, a team led by investigators at the University of California, Los Angeles, isolated tau tangles from postmortem brain tissue donated by people who had Alzheimer’s. The tangles were treated with EGCG and flash frozen. Images of the EGCG and tau fiber complexes were captured with a technique called cryogenic electron microscopy.
These EGCG-tau fiber images helped reveal how EGCG attaches to and dismantles the tau fibers. According to the team’s model, EGCG binds to clefts, or openings, along each layer of the fibers, destabilizing the layers and slowly prying the fibers apart.
Using computer simulations, the researchers identified other molecules likely to work in a similar way as EGCG but that may be able to enter the brain more easily. They tested these other molecules in a cell model for tau tangle formation and additionally on tau tangles isolated from brain samples donated by Alzheimer’s patients after death. In both setups, several of the molecules untangled tau fibers. Although researchers caution that more work is needed, the experiments indicated that certain molecules also prevented the untangled tau from spreading and forming new tangles.
Overall, the findings suggest that these newly discovered molecules that can penetrate the brain and dismantle tau tangles may be a promising strategy for treating Alzheimer’s. Future research into these molecules may help uncover more about their therapeutic potential.
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