4.2.2. Alzheimer Disease

As a model for Alzheimer disease, different transgenic kinds of mice have been studied to observe effects of DHA or its derivatives. In a triple-transgenic mouse model of Alzheimer disease, neuroprotection D1 (NPD1) (50 nM) downregulates Aβ42-induced expression of COX-2, TNF-α, and B-94, a TNF-α-inducible pro-inflammatory element [37]. Increasing brain DHA level after intracerebroventricular amyloid-β infusion led to a decrease in Iba-1 microglial cells counted in fat-1 mice and lower degenerative neurons in mice supplemented with fish oil containing 1.5% DHA (among other fatty acids). Authors also observed significantly higher branching complexity (CA1, CA3, and dentate gyrus) in fat-1 and wild type mice fed with fish oil than in wild type mice fed with safflower oil. These results suggest that dietary supplement in fatty acids, including DHA decreased microglial responses to amyloid-β infusion [38]. In another model of AD mice, induced by co-administration of D-galactose and aluminium chloride, supplementation with DHA (200 mg/kg) + EGb761 (*Ginkgo biloba* standardized extract) enhanced behavioral recovery and protein phosphatase 2A expression, a major protein phosphatase of tau in the brain, while it downregulated TNF-α expression (both in the hippocampus, CA3) [39]. Sharman et al. tried a different combination of supplements instead of using DHA, ALA (α-lipoic acid), epigallocatechin-3-gallate, or curcumin alone. Reductions in amyloid plaque load, microglial activation, Aβ40/Aβ42 levels, and memory deficits in male Tg2576 mice (a familial AD model) have been observed by using a combination of EGCG, DHA (50 mg/kg body weight), and ALA [41].

Surprisingly, TgCRND8 mice (transgenic mice model for AD) supplemented with 0.246% of DHA (wt/wt) in a whole-food diet, exhibited higher TNF-α expression compared with control groups, corresponding with observed behavioral impairment [40].
