The isoform-specific pathological effects of apoE4 in vivo are prevented by a fish oil (DHA) diet and are modified by cholesterol.
Transgenic mice which express either the Alzheimer's disease risk factor apoE4 or its benign form apoE3 were subjected to fish-oil, high cholesterol and control diets for three months starting at weaning. This was followed by an examination of the extent to which the effects of the diets on brain lipids can be modified by diet and by complimentary assessments of the extent to which the pathological effects of apoE4 can be modulated by diet. Brain lipid composition was affected by fish oil (DHA) and cholesterol diets and by environmental conditions. In contrast, the levels of these brain lipids were not markedly affected byapoE4. ApoE4 elevated the levels of the neurotoxic peptide amyloid-beta β (Aβ). This effect was accompanied with neuronal and behavioural impairments. Importantly, all of these apoE4 phenotypes were abolished by the fish oil (DHA) diet, whereas the cholesterol diet modified them. These findings suggest that a fish oil (DHA) diet could be used to attenuate the effects of apoE4 in AD.