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

Extracellular plaques of β-amyloid (Aβ) peptides are implicated in Alzheimer's Disease (AD) pathogenesis. Aβ formation is precluded by α-secretase, which cleaves within the Aβ domain of APP generating soluble APP-α (sAPP-α). Thus, α-secretase upregulation may be a target AD therapy. We previously showed green tea derived EGCG increased sAPP-α 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 (8 mg/kg/day) and EGCG (62.5 mg/kg/day or 12.5 mg/kg/day) would reduce AD-like pathology in Tg2576 mice. In vitro co-treatment of N2a cells with fish oil and EGCG enhanced sAPP-α 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 Aβ deposits (P < 0.001) suggesting moderate supplementation with EGCG and fish oil having significant therapeutic potential for the treatment of AD.