For the neuropsychological and clinical correlations of the representative neural circuits, our findings suggest that all the key nodes and structural connectivity (especially axonal integrity) of both frontostrial and hippocampus-PCC circuits are involved in general cognitive function and disease severity in FAD, and the presymptomatic involvement of the frontostriatal circuit structure in general cognitive function is disrupted in APP mutation carriers. The gene discussed is APP; the disease is familial Alzheimer disease.