Brain region-dependent increases in β-amyloid and apolipoprotein E levels in hypercholesterolemic rabbits

Recent studies indicate a possible link between serum cholesterol level, beta-amyloid (Abeta) peptide concentrations, and the incidence of Alzheimer's disease (AD). In the present report, the effects of dietary cholesterol on Abeta and apolipoprotein E (APOE) levels in several brain regions were examined using diet-induced hypercholesterolemic rabbits as the animal model. Increased dietary cholesterol levels increased Abeta concentrations in temporal cortex (p = 0.02). A similar trend was observed in the frontal cortex (p = 0.06), yet not in the cerebellum. Interestingly, the regional levels of Abeta in the hypercholesterolemic rabbit paralleled the amyloid pathology observed in AD brain. Elevated APOE levels were also noticed in temporal (p < 0.01) and frontal (p < 0.01) cortices, but not in cerebellum, in the rabbit fed with cholesterol-abundant diet. These results suggest that high serum cholesterol levels could induce the elevation of brain APOE, which may play a role in aggravating the Abeta accumulation.