IDENTIFICATION AND ANALYSIS OF CRITICAL GENES IN EARLY-ONSET ALZHEIMER\'S DISEASE AND RELATED UNDERLYING DISEASES Abstract Background: Alzheimer's Disease (AD) is a neurodegenerative and multifactorial disorder. The investigation of the key genes and metabolic pathways is important to understanding the mechanism of AD. This study aimed to analyze the gene network and biological pathways of AD using bioinformatics approaches. Materials and methods: AD genes were identified and a gene network was constructed using the STRING. Network analysis was performed to identify functional modules and key genes related to AD by Cytoscape and investigate their gene ontology using the g: Profiler. Results: By network clustering, five functional modules were identified, which play an important role in amyloidbeta formation, protein metabolic process, and response to organic substance. APOE, TREM2, SORL1, BIN1, PICALM, ABCA7, CD2AP, CD33, MS4A6A, and CLU, were found as key genes in AD. These genes play roles in the negative regulation of amyloid precursor protein catabolic process. A significant function of these genes is amyloid-beta binding and localized mostly in a somatodendritic compartment. Four key genes that contain APOE, SORL1, ABCA7, and TREM2 are Early-Onset Alzheimer's Disease (EOAD) genes and have a critical role in AD. In addition, APOE and SORL1 genes, play an indirect role in AD at a young age through the underlying diseases like obesity, hypercholesterolemia, diabetes mellitus, and hypertensive. Conclusion: The results of the present study showed some of the underlying diseases are related to EOAD, and control of them can prevent the early occurrence of AD. These results can provide novel insights into the pathogenesis and treatment of AD.