Green and Black Tea Polyphenols Mechanistically Inhibit the Aggregation of Amyloid-β in Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is the 6th leading cause of death and is the only disease among the top 10 that cannot be prevented, cured or treated. The amyloid cascade hypothesis states that naturally occurring amyloid-β (Aβ) monomer aggregates via a nucleation-dependent pathway to form soluble aggregates and insoluble fibrils that deposit as plaques in the brain. Consequently, inhibition of Aβ aggregation is one therapeutic strategy for AD. This study sought to explain epidemiological correlations between frequent tea consumption and reduced incidence of AD by identifying the Aβ aggregation inhibitory capabilities of key polyphenol components in green and black tea.Polyphenols studied include green tea catechins, epicatechin, epigallocatechin and epigallocatechin gallate, as well as black tea theaflavins, theaflavin and theaflavin monogallate. Four assays were used to target unique steps along the aggregation pathway: a monomer aggregation assay to monitor the overall aggregation process; an oligomerization assay to monitor the initial nucleation step; an association assay to monitor the late stage lateral binding of soluble aggregates; and an elongation assay to monitor the late stage lengthening of soluble aggregates.Catechins and theaflavins show different inhibitory capabilities at varying mechanistic steps of the Aβ aggregation pathway. Catechins affect only the later stages of aggregation, suggesting that catechins may bind a specific structure present in aggregates. Conversely, theaflavins show inhibitory capabilities at every stage of aggregation, alluding to a sequence specific recognition. Furthermore, better inhibitory capabilities, for both polyphenol categories, can be correlated with the number of gallate groups.