Identification of Critical Genes and Underlying Diseases in Early-onset Alzheimer’s Disease by Bioinformatics Approach

Background: Alzheimer’s disease (AD) is a neurodegenerative and multifactorial disorder. Investigating the key genes and metabolic pathways is important for understanding the mechanisms of AD. This study aimed to analyze the gene network and biological pathways of AD using bioinformatics approaches.  Materials and Methods: AD-related genes were identified, and a gene network was constructed using STRING. Network analysis was performed to identify functional modules and key genes related to AD using Cytoscape, and gene ontology was investigated using g:Profiler.  Results: Through network clustering, five functional modules were identified, which play important roles in amyloid-beta formation, protein metabolic processes, and responses to organic substances. Key genes in AD included APOE, TREM۲, SORL۱, BIN۱, PICALM, ABCA۷, CD۲AP, CD۳۳, MS۴A۶A, and CLU. 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 they are mostly localized in the somatodendritic compartment. Four key genes—APOE, SORL۱, ABCA۷, and TREM۲—are associated with early-onset AD (EOAD) and play critical roles in AD. Additionally, the APOE and SORL۱ genes have an indirect role in AD at a young age through underlying diseases such as obesity, hypercholesterolemia, diabetes mellitus, and hypertension.  Conclusion: Some underlying diseases are related to EOAD, and controlling these conditions may prevent the early onset of AD. These results can provide novel insights into the pathogenesis and treatment of AD.

Keywords:

Early-onset alzheimer’s disease , System biology , Underlying diseases , Key gene