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Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice.

The Journal of neuroscience : the official journal of the Society for Neuroscience (2005-09-24)
Kavon Rezai-Zadeh, Doug Shytle, Nan Sun, Takashi Mori, Huayan Hou, Deborah Jeanniton, Jared Ehrhart, Kirk Townsend, Jin Zeng, David Morgan, John Hardy, Terrence Town, Jun Tan
ABSTRACT

Alzheimer's disease (AD) is a progressive neurodegenerative disorder pathologically characterized by deposition of beta-amyloid (Abeta) peptides as senile plaques in the brain. Recent studies suggest that green tea flavonoids may be used for the prevention and treatment of a variety of neurodegenerative diseases. Here, we report that (-)-epigallocatechin-3-gallate (EGCG), the main polyphenolic constituent of green tea, reduces Abeta generation in both murine neuron-like cells (N2a) transfected with the human "Swedish" mutant amyloid precursor protein (APP) and in primary neurons derived from Swedish mutant APP-overexpressing mice (Tg APPsw line 2576). In concert with these observations, we find that EGCG markedly promotes cleavage of the alpha-C-terminal fragment of APP and elevates the N-terminal APP cleavage product, soluble APP-alpha. These cleavage events are associated with elevated alpha-secretase activity and enhanced hydrolysis of tumor necrosis factor alpha-converting enzyme, a primary candidate alpha-secretase. As a validation of these findings in vivo, we treated Tg APPsw transgenic mice overproducing Abeta with EGCG and found decreased Abeta levels and plaques associated with promotion of the nonamyloidogenic alpha-secretase proteolytic pathway. These data raise the possibility that EGCG dietary supplementation may provide effective prophylaxis for AD.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
(−)-Epigallocatechin gallate, ≥95%
Sigma-Aldrich
(−)-Epigallocatechin gallate, ≥80% (HPLC), from green tea
Sigma-Aldrich
Anti-APP A4 Antibody, a.a. 66-81 of APP {NT}, clone 22C11, clone 22C11, Chemicon®, from mouse
Supelco
(−)-Epigallocatechin gallate, analytical standard
Sigma-Aldrich
Monoclonal Anti-β-Amyloid antibody produced in mouse, clone BAM-10, ascites fluid
Epigallocatechin gallate, primary reference standard

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