Introduction: Profiling the spatial-temporal expression pattern and characterizing the regulatory net-works of brain tissues are vital for understanding the pathophysiology of Alzheimer’s disease (AD).Methods: We performed a systematic integrated analysis of expression profiles of AD-affected braintissues(684ADand562controls).Anetwork-basedconvergentfunctionalgenomicapproachwasusedto prioritize possible regulator genes during AD development, followed by functional characterization.Results: We generated a complete list of differentially expressed genes and hub genes of the tran-scriptomic network in AD brain and constructed a Web server (www.alzdata.org) for public access.Seventeen hub genes active at the early stages, especially YAP1, were recognized as upstream regu-lators of the AD network. Cellular assays proved that early alteration of YAP1 could promote AD byinfluencing the whole transcriptional network.Discussion: Early expression disturbance of hub genes is an important feature of AD development,and interfering with this process may reverse the disease progression.