Objective      To determine the effect of different genotypes of apolipoprotein E (APOE) on the axonal growth and investigate the possible underlying mechanism.       Methods      Cortical neurons from new born wild type mice or APOE gene knockout mice (APOE

-

) were isolated and cultured primarily in vitro. The recombinant human ApoE2

ApoE3 and ApoE4 proteins were added into the culture medium of APOE

-

neurons respectively

thereby the cultured neurons were divided into 5 groups

namely WT group (wild type mice)

ApoE

-

group

ApoE2 group

ApoE3 group and ApoE4 group. The length of axons and neurites number was measured by phase contrast microscopy. The axons were labeled by immunofluorescence staining to measure the fluorescence intensity of axons. The effect of different ApoE proteins on the expression of cell division cycle 42 (cdc42) was determined by Western blotting.       Results      The average length of axons was significantly longer in the WT

ApoE2 and ApoE3 groups than ApoE

-

and ApoE4 groups (

P

0.05). The average number of neurites was 3.80±0.84

3.60±0.55

and 3.40±1.14

respectively for WT

ApoE2 and ApoE3 groups

markedly larger than those of ApoE

-

group (1.80±0.45) and ApoE4 group(1.90±0.84

P

0.05). The axonal fluorescence intensity of WT

ApoE2 and ApoE3 groups was 54.10±7.32

52.40±6.33

and 50.50±8.21

respectively

obviously higher than the ApoE

-

(37.20±9.30) and ApoE4 groups (39.00±8.32

P

0.05). The expression of cdc42 was significantly higher in WT

ApoE2 and ApoE3 groups than ApoE

-

and ApoE4 groups (

P

0.05). There was no significant difference among WT

ApoE2 and ApoE3 groups

and between ApoE

-

and ApoE4 groups（

P

0.05）.       Conclusion      The growth of neurons axons is differently affected by ApoE isoforms

and so is the expression of tubulinⅢ and cdc42

which maybe one of the mechanisms of effect of ApoE isoforms on the growth of neurons axons.