Latifi-Navid Hamid, Mokhtari Saeedeh, Taghizadeh Sepideh, Moradi Fatemeh, Poostforoush-Fard Dorsa, Alijanpour Sakineh, Aghanoori Mohamad-Reza
Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran; School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran; Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Iran.
Department of Stem Cells and Regenerative Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Biochim Biophys Acta Mol Basis Dis. 2025 Oct;1871(7):167925. doi: 10.1016/j.bbadis.2025.167925. Epub 2025 May 27.
Alzheimer's Disease (AD) is the most prevalent neurodegenerative disorder, characterized by progressive cognitive decline. Early and accurate diagnosis is crucial for improving patient outcomes, yet current diagnostic methods remain invasive, costly, and limited in accessibility. This study leverages artificial intelligence (AI) and machine learning approaches to perform a multi-omics analysis, integrating proteomics and transcriptomics data to identify potential biomarkers for early AD prediction. Using multiple AD-related databases and AI-powered literature review tools, we extracted and analyzed gene expression profiles from various tissues, including brain, cerebrospinal fluid (CSF), and plasma. A protein-protein interaction (PPI) network was reconstructed to determine key hub genes using centrality analysis. Our findings revealed 13 common hub genes, including APP, YWHAE, YWHAH, SOD1, UQCRFS1, ATP5F1B, AP2M1, MMAB, INA, RPL6, HADHB, CD63, and CTNNB1, that are significantly implicated in both early and advanced AD. Furthermore, pathway enrichment analysis identified critical pathways such as oxidative phosphorylation, metabolic pathways, and synaptic transmission, which are associated with AD progression. Additionally, nine common miRNAs and eight key molecular axes were determined, highlighting potential mechanistic links between early and advanced AD. These findings offer novel insights into AD pathophysiology and provide a foundation for developing non-invasive biomarkers for early detection. Future experimental validation of these biomarkers is essential to translate these findings into clinical applications.
阿尔茨海默病(AD)是最常见的神经退行性疾病,其特征为进行性认知衰退。早期准确诊断对于改善患者预后至关重要,但目前的诊断方法仍然具有侵入性、成本高昂且可及性有限。本研究利用人工智能(AI)和机器学习方法进行多组学分析,整合蛋白质组学和转录组学数据,以识别早期AD预测的潜在生物标志物。使用多个与AD相关的数据库和人工智能驱动的文献综述工具,我们从包括大脑、脑脊液(CSF)和血浆在内的各种组织中提取并分析了基因表达谱。利用中心性分析重建了蛋白质-蛋白质相互作用(PPI)网络,以确定关键枢纽基因。我们的研究结果揭示了13个常见的枢纽基因,包括APP、YWHAE、YWHAH、SOD1、UQCRFS1、ATP5F1B、AP2M1、MMAB、INA、RPL6、HADHB、CD63和CTNNB1,它们在早期和晚期AD中均有显著关联。此外,通路富集分析确定了关键通路,如氧化磷酸化、代谢通路和突触传递,这些通路与AD进展相关。此外,还确定了9个常见的miRNA和8个关键分子轴,突出了早期和晚期AD之间潜在的机制联系。这些发现为AD病理生理学提供了新的见解,并为开发用于早期检测的非侵入性生物标志物奠定了基础。这些生物标志物未来的实验验证对于将这些发现转化为临床应用至关重要。