title: Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice.
abstract: We previously reported that intraperitoneal (i.p.) injection (20 mg/kg) of (-)-epigallocatechin-3-gallate (EGCG), the main polyphenolic constituent of green tea, decreased beta-amyloid (Abeta) levels and plaques via promotion of the non-amyloidogenic alpha-secretase proteolytic pathway in "Swedish" mutant amyloid precursor protein overexpressing (APPsw, Tg) mice. Here, we find that EGCG administered orally in drinking water (50 mg/kg) similarly reduces Abeta deposition in these mice. Following a six month treatment of an 8 month old cohort, immunohistochemical analysis of coronal sections reveals that plaque burdens were reduced in the cingulate cortex, hippocampus, and entorhinal cortex by 54%, 43%, and 51%, respectively. Congo red plaque burdens were decreased in the cingulate cortex, hippocampus, and entorhinal cortex by 53%, 53%, and 58%, respectively as well. ELISA of brain homogenates of the treatment Tg mice revealed consistent reductions in both Abeta1-40 and 1-42 soluble and insoluble forms. In the present study we also investigated the effect EGCG administration had on tau pathology and cognition in Tg mice. Both i.p. and orally-treated Tg animals were found to have modulated tau profiles, with markedly suppressed sarkosyl-soluble phosphorylated tau isoforms. Radial arm water maze (RAWM) testing for working memory indicated that EGCG provided cognitive benefit to Tg mice with both i.p. and oral administration, although i.p.-treated animals showed a more pronounced benefit because of the greater impairment of their Tg controls at the time of testing. Taken together, these data further the notion of EGCG dietary supplementation as a potentially safe and effective prophylaxis for Alzheimer's disease.
authors.affiliation: Rashid Laboratory for Developmental Neurobiology, Silver Child Development Center, Department of Psychiatry and Behavioral Medicine, and Department of Neurosurgery, University of South Florida, Tampa, FL 33613, USA.
authors.forename: Kavon
authors.initials: K
authors.lastname: Rezai-Zadeh
authors.forename: Gary W
authors.initials: GW
authors.lastname: Arendash
authors.forename: Huayan
authors.initials: H
authors.lastname: Hou
authors.forename: Frank
authors.initials: F
authors.lastname: Fernandez
authors.forename: Maren
authors.initials: M
authors.lastname: Jensen
authors.forename: Melissa
authors.initials: M
authors.lastname: Runfeldt
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Shytle
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018696:Neuroprotective Agents; D016875:tau Proteins; D002392:Catechin; C045651:epigallocatechin gallate