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Khorammi M, Bosstaghzadeh F, Golbashirzadeh M. Deciphering APOE Gene Interaction Networks in Alzheimer’s Disease: A Comprehensive Analysis of Genetic Factors and Their Potential as Therapeutic Targets. Res Mol Med (RMM) 2024; 12 (3) :75-92
URL: http://rmm.mazums.ac.ir/article-1-580-en.html

Background: Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by progressive cognitive decline. The apolipoprotein E (APOE) gene, particularly its ε4 allele, is a wellestablished genetic risk factor for late-onset AD. This study aimed to decipher APOE’s interaction
networks to advance AD diagnostics and therapeutics.

Methods: We conducted an analytical study comparing gene expression data and genetic factors between AD patients and healthy controls. Candidate genes were identified through comprehensive literature reviews and bioinformatics database searches, prioritizing genes validated by in vivo, in vitro, or in silico evidence. Interaction networks were constructed using MATLAB software, version R2025a and R software, version 4.5.1.

Results: Network analysis of AD-associated proteins—using centrality measures (maximum neighborhood component (MNC), degree, betweenness, closeness, and radiality)—identified TREM2, BDNF, NCSRN, SORL1, and TNF as key components within the APOE network. TREM2 and TNF regulate neuroinflammatory responses, BDNF supports neurotrophic activity and synaptic plasticity, NCSRN modulates Notch signaling, and SORL1 is critical for amyloid-beta (Aβ) metabolism. These findings highlight AD’s multifactorial nature and reveal potential therapeutic targets and biomarkers.
Conclusion: Our results align with prior research, reinforcing the roles of TREM2 (microglial activity), BDNF (neuroprotection), NCSRN (signaling pathways), and SORL1 (Aβ regulation) in AD pathogenesis. By mapping APOE’s interaction network, this study provides a foundation for future therapeutic innovations.