The morphological and biochemical studies of the hippocampal CA1 area in ApoE-deficient mice under the conditions of dietary intake (8 weeks) with low (LF) and high (HF) fat content were performed. Methods of immunohistochemistry, light and electron microscopy, immunoassay and morphometric as well as statistical analyses were used. It was revealed that the morpho-functional state of the nerve cells of the hippocampus ApoE-/- mice highly depends on the fat content of the diet. A higher degree of neuroinflammation was observed in the LF-group than in the control and HF-groups, which was manifested in reactive astro- and microgliosis. The number of undamaged pyramidal neurons in the CA1 area of the hippocampus ApoE-/- mice in the LF-group significantly decreased compared to the control group and the HF-group. In animals with LF- and HF-diet the density of synaptic terminals, the number of mitochondria in them, as well as the concentration of cellular adhesion molecules were decreased. It was suggested that synaptogenesis and synaptic plasticity in higher degree depended on the shortage of аpolipoprotein E than on the fat content in the diet.