Green Tea Extract EGCG Blocks Amyloid Plaque Formation in Brain Cell Cultures

The green tea extract, (−)-epigallocatechin-3-gallate (EGCG) prevented formation of metal-associated amyloid-beta plaques in brain cell cultures and dissolved plaques that had already formed.

EGCG is the most abundant catechin in tea and is a potent antioxidant that may have therapeutic applications in the treatment of many disorders. It is found in green tea but not black tea.

Alzheimer's disease investigators at the University of Michigan (Ann Arbor, USA) investigated and compared the interaction and reactivity of EGCG with metal (copper and zinc) and metal-free A-beta species. Such a study was considered necessary, as chelation therapy, which involves the removal of heavy metals from the body, has been shown to be beneficial in lowering amyloid plaque levels. This is because A-beta aggregation is somewhat dependent on the metal ions copper and zinc, and A-beta deposition was impeded in transgenic mice treated with the antibiotic clioquinol, a known copper/zinc chelator.

In the current study, a team comprising chemists, biochemists, and biophysicists used advanced analytical techniques including ion mobility-mass spectrometry (IM-MS), two-dimensional NMR spectroscopy, and computational methods to study the interaction of EGCG and A-beta plaques in cultures of human brain cells.

They reported in the February 20, 2013, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that EGCG interacted with metal-A-beta species and formed small, unstructured A-beta aggregates more noticeably than in metal-free conditions. Incubation of cells with EGCG eliminated the toxicity presented by both metal-free A-beta and metal-A-beta plaques. EGCG bound to A-beta monomers and dimers, generating more compact peptide conformations than those from EGCG-untreated A-beta species and nontoxic ternary EGCG-metal-A-beta complexes were produced.

"A lot of people are very excited about this molecule," said senior author Dr. Mi Hee Lim, assistant professor of chemistry at the University of Michigan. "We used a multidisciplinary approach. This is the first example of structure-centric, multidisciplinary investigations by three principal investigators with three different areas of expertise. But we believe you have to have a lot of approaches working together, because the brain is very complex. We want to modify them [molecules like EGCG] for the brain, specifically to interfere with the plaques associated with Alzheimer's."

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