Few works studied the directed whole-brain interaction between different brain regions of Alzheimer's disease (AD). Here, we investigated the whole-brain effective connectivity and studied the graph metrics associated with AD. Large-scale Granger causality analysis was conducted to explore abnormal whole-brain effective connectivity of patients with AD. Moreover, graph-theoretical metrics including smallworldness, assortativity, and hierarchy, were computed from the effective connectivity network. Statistical analysis identified the aberrant network properties of AD subjects when compared against healthy controls. Decreased small-worldness, and increased characteristic path length, disassortativity, and hierarchy were found in AD subjects. This work sheds insight into the underlying neuropathological mechanism of the brain network of AD individuals such as less efficient information transmission and reduced resilience to a random or targeted attack.