New Weapons to Fight Alzheimer's?

By Jane Farrell

Researchers have discovered how a molecule found in green tea breaks apart tangles of the protein tau, a hallmark of Alzheimer’s disease. Based on this finding, the team identified other molecules that can also untangle tau and may be even better drug candidates than the green tea molecule.

Results from the study, funded in part by the National Institute on Aging (NIA), were published in Nature Communications.

In Alzheimer’s, tau abnormally sticks together in fibrous tangles that spread between brain cells, leading to cell death. A molecule known as epigallocatechin gallate (EGCG) — the one found in green tea — is known to untangle tau fibers. However, EGCG is not on its own an effective Alzheimer’s treatment because it cannot easily penetrate the brain and binds to many proteins other than tau, weakening its effect.

Therefore, researchers wanted to find molecules that replicate the effects of EGCG but have better drug properties for treating Alzheimer’s. 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.

A NIA news release detailed how the researchers, using computer simulations, identified other molecules likely to work in the same way as EGCG but may be able to enter the brain more easily.

The researchers 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.