Differentiated N2a cells expressing ApoE2 displayed the most potent hexokinase expression and glycolytic activity. A, B, N2a cell morphology was evaluated by phase contrast imaging. The formation of neuronal processes were observed after RA incubation for 96 h. Scale bar = 40 μm. C–E, The differentiation of N2a cells was also confirmed by immunoblotting for markers of mature neurons. Expressions of NeuN, synaptophysin, and PSD95 were significantly increased in the differentiated N2a cells. n = 3–8 per group. F, ApoE expression levels were comparable in differentiated N2a cells transfected with ApoE isoforms. n = 6 per group. G, H, Protein expressions of Hk1 1 and Hk2 were significantly higher in neuron-like differentiated N2a cells expressing ApoE2. n = 7–13 per group. I, J, Differentiated N2a cells expressing ApoE2 exhibited the most potent hexokinase activity and glycolytic function. Results were normalized to ApoE3 group. n = 3–6 per group. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001 by one-way ANOVA with Bonferroni post hoc test.