en بیوانفورماتیک Bioinformatic پژوهشي Research <div style="text-align: justify;"><strong>Background</strong>: Alzheimer&rsquo;s disease (AD) is a prevalent neurodegenerative disorder characterized by progressive cognitive decline. The apolipoprotein E (APOE) gene, particularly its &epsilon;4 allele, is a well-established genetic risk factor for late-onset AD. This study aimed to decipher APOE&rsquo;s interaction networks to advance AD diagnostics and therapeutics.<br> <strong>Materials and Methods</strong>: 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.<br> <strong>Results</strong>: Network analysis of AD-associated proteins&mdash;using centrality measures (maximum neighborhood component (MNC), degree, betweenness, closeness, and radiality)&mdash;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 (A&beta;) metabolism. These findings highlight AD&rsquo;s multifactorial nature and reveal potential therapeutic targets and biomarkers.<br> <strong>Conclusion</strong>: Our results align with prior research, reinforcing the roles of TREM2 (microglial activity), BDNF (neuroprotection), NCSRN (signaling pathways), and SORL1 (A&beta; regulation) in AD pathogenesis. By mapping APOE&rsquo;s interaction network, this study provides a foundation for future therapeutic innovations.</div> Alzheimer’s disease (AD), BACE1, Amyloid-beta (Aβ), Amyloid precursor protein (APP), Therapeutic strategies 75 92 http://rmm.mazums.ac.ir/browse.php?a_code=A-10-1382-1&slc_lang=en&sid=1 Mahshid Khorrami golimori1984@gmail.com 100319475328460012980 100319475328460012980 No Department of Biology, Dez. C., Islamic Azad University, Dezful, Iran. Fatemeh Bossaghzadeh bossagh_f_1359@yahoo.com 100319475328460012981 100319475328460012981 Yes Department of Biology, Dez. C., Islamic Azad University, Dezful, Iran. Morteza Golbashirzadeh m.golbashir@gmail.com 100319475328460012982 100319475328460012982 No Department of Pharmaceutical Biotechnology, Chabahar Faculty of Medical Science, Chabahar, Iran.