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Epidemiological and clinical trial findings suggest that consumption of docosahexaenoic acid (DHA) lowers the risk of Alzhemier's disease (AD). We examined the effects of short‐term (3 months) DHA enriched diet on plaque deposition and synaptic deficts in forebrain of young APPswe/PS1ΔE9 transgenic (tg) and non‐transgenic (ntg) mice. Gas chromatography revealed a significant increase in DHA concomitant with a decrease of arachidonic acid in both brain and liver in mice fed with DHA. Female tg mice consumed relatively more food daily than ntg female mice, independent of diet. Plaque load was significantly reduced in the cortex, ventral hippocampus and striatum of female APPswe/PS1ΔE9 tg mice on DHA diet compared to female tg mice on control diet. Immunoblot quantitation of the APOE receptor, LR11, which is involved in APP trafficking and Aβ production, were unchanged in mice on DHA or …