Alzheimer’s disease is a primary age-related neurodegenerative disorder that can result in impaired cognitive and memory functions. Al-though connections between changes in brain networks of Alzheimer’s disease patients have been established, the mechanisms that drive these alterations remain incompletely understood. This study, which was conducted in 2018 at Northeast University in China, included data from 97 participants of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset covering genetics, imaging, and clinical data. All participants were divided into two groups: normal control (n = 52; 20 males and 32 females; mean age 73.90 ± 4.72 years) and Alzhei-mer’s disease (n = 45, 23 males and 22 females; mean age 74.85 ± 5.66). To uncover the wiring mechanisms that shaped changes in the topology of human brain networks of Alzheimer’s disease patients, we proposed a local na?ve Bayes brain network model based on graph theory. Our results showed that the proposed model provided an excellent fit to observe networks in all properties examined, including clustering coefficient, modularity, characteristic path length, network efficiency, betweenness, and degree distribution compared with empirical methods. This proposed model simulated the wiring changes in human brain networks between controls and Alzheimer’s dis-ease patients. Our results demonstrate its utility in understanding relationships between brain tissue structure and cognitive or behavioral functions. The ADNI was performed in accordance with the Good Clinical Practice guidelines, US 21CFR Part 50–Protection of Human Subjects, and Part 56–Institutional Review Boards (IRBs)/Research Good Clinical Practice guidelines Institutional Review Boards (IRBs)/Research Ethics Boards (REBs).