Fish oil enhances anti-amyloidogenic properties of green tea EGCG in Tg2576 mice

Neurosci Lett. 2010 Mar 8;471(3):134-8. doi: 10.1016/j.neulet.2010.01.026. Epub 2010 Jan 22.

Abstract

Extracellular plaques of beta-amyloid (Abeta) peptides are implicated in Alzheimer's Disease (AD) pathogenesis. Abeta formation is precluded by alpha-secretase, which cleaves within the Abeta domain of APP generating soluble APP-alpha (sAPP-alpha). Thus, alpha-secretase upregulation may be a target AD therapy. We previously showed green tea derived EGCG increased sAPP-alpha in AD mouse models. However, the comparable effective dose of EGCG in humans may exceed clinical convenience and/or safety. Epidemiological studies suggested fish oil consumption is associated with reduced dementia risk. Here we investigated whether oral co-treatment with fish oil (8mg/kg/day) and EGCG (62.5mg/kg/day or 12.5mg/kg/day) would reduce AD-like pathology in Tg2576 mice. In vitro co-treatment of N2a cells with fish oil and EGCG enhanced sAPP-alpha production compared to either compound alone (P<0.001). Fish oil enhanced bioavailability of EGCG versus EGCG treatment alone (P<0.001). Fish oil and EGCG had a synergetic effect on inhibition of cerebral Abeta deposits (P<0.001) suggesting moderate supplementation with EGCG and fish oil having significant therapeutic potential for the treatment of AD.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Biological Availability
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Catechin / analogs & derivatives*
  • Catechin / pharmacokinetics
  • Catechin / pharmacology
  • Catechin / therapeutic use
  • Cell Line, Tumor
  • Drug Synergism
  • Female
  • Fish Oils / pharmacokinetics
  • Fish Oils / pharmacology*
  • Fish Oils / therapeutic use
  • Mice
  • Mice, Transgenic
  • Tea*

Substances

  • Amyloid
  • Amyloid beta-Protein Precursor
  • Fish Oils
  • Tea
  • Catechin
  • epigallocatechin gallate