To identify the relationship between the topological properties and glutamate in genetic-related subgroups (ApoE4 carriers and non-ApoE4 carriers), combined resting state fMRI (rs-fMRI) and MRS were applied in this study. Graph theory metrics of subgroups were calculated and compared. In the results, ApoE4 carriers had worse network segregation and integration. However, there was significant correlation between [Glx]abs in left hippocampus and topological metrics in high-risk group. We postulated that glutamatergic synaptic transmission modulates rs-fMRI activities in ApoE4 carriers.