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Background : The pathogenesis of Alzheimer’s disease (AD) remains to be elucidated. This study aimed to identify the hub genes in AD pathogenesis and determine their functions and pathways.   Methods : A co-expression network for an AD gene dataset with 401 samples was constructed, and the AD status-related genes were screened. The hub genes of the network were identified and validated by an independent cohort. The functional pathways of hub genes were analyzed.   Results : The co-expression network revealed a module that related to the AD status, and 101 status-related genes were screened from the trait-related module. Gene enrichment analysis indicated that these status-related genes are involved in synaptic processes and pathways. Four hub genes ( ENO2 ,  ELAVL4 ,  SNAP91 , and  NEFM ) were identified from the module, and these hub genes all participated in AD-related pathways, but the associations of each gene with clinical features were variable. An independent dataset confirmed the different expression of hub genes between AD and controls.   Conclusions : Four novel genes associated with AD pathogenesis were identified and validated, which provided novel therapeutic targets for AD.

Co-expression Network Analysis Reveals Novel Genes Underlying Alzheimer’s Disease Pathogenesis