The green tea polyphenol (-)-epigallocatechin gallate prevents the aggregation of tau protein into toxic oligomers at substoichiometric ratios

The accumulation of amyloid-beta (Ab) and tau aggregates is a pathological hallmark of Alzheimer's disease. Both polypeptides form fibrillar deposits, but several lines of evidence indicate that Ab and tau form toxic oligomeric aggregation intermediates. Depleting such structures could thus be a powerful therapeutic strategy. We generated a fragment of tau (His-K18 Delta K280) that forms stable, toxic, oligomeric tau aggregates in vitro. We show that (-)-epigallocatechin gallate (EGCG), a green tea polyphenol that was previously found to reduce Ab aggregation, inhibits the aggregation of tau K18 Delta K280 into toxic oligomers at ten-to hundred-fold substoichiometric concentrations, thereby rescuing toxicity in neuronal model cells. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.