Objective        To determine the effect of different ApoE subtypes on the growth cones of neuronal axons.       Methods        Cortical explants were isolated from 1-day-old ApoE knockout mice

and then cultured in vitro with the treatment of the recombinant human ApoE2

3 and 4 (20 μg/ml) respectively for 24 h. Immunofluorescence staining and Western blot analysis were used to detect recombinant human ApoE whether entering axons and growth cones. Phalloidin staining was used to dye the growth cones after ApoE2

3

and 4 treatment. Extracellular signal-regulated kinase (ERK) inhibitor was added into culture medium to discover ERK pathway whether participating in the process of ApoE subtypes influencing the growth cones.       Results        Immunofluorescence staining and Western blotting showed the recombinant human ApoE was positive in the axons and growth cones

and the fluorescence intensity of axonal growth cones was 50.7±19.4

58.5±15.4 and 23.4±13.5

respectively for ApoE2

3 and 4 treatment. The fluorescence intensity of axonal growth cones with ApoE4 treatment was significantly weaker than that of growth cones after ApoE2 or ApoE3 treatment（P0.05）. The fluorescence intensity of growth cones in cortical explants with ApoE4 and ERK inhibitor treatment was 32.8±13.2

but that of growth cones after ApoE4 treatment was 21.9±6.9. The fluorescence intensity in experimental group was stronger than that in control group without above inhibitor（P0.05）.       Conclusion        Recombinant human ApoE can enter the axons and growth cones of explants. ApoE4 can negatively influence the growth of growth cones

which is inhibited by ERK inhibitor.