Identifying Alzheimer's disease-associated genes related to N6-methyladenosine modification as potential biomarkers through correlation analysis: A retrospective observational studyLin Yang a 1, Pengtao Zheng a 1, Cong Huang b, Chonghao Gao a, Xinping Pang c, Hui Liu b, Yanyu Wei d, Chaoyang Pang a a College of Computer Science, Sichuan Normal University, Chengdu, Sichuan Province, China b School of Information and Software Engineering, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China c School of Science, Xi’an Jiaotong-Liverpool University, Suzhou, Jiangsu Province, China d National Key Laboratory of Science and Technology on Vacuum Electronics, School of Electronic Science and Engineering, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China Received 27 December 2024, Accepted 13 January 2025, Available online 26 January 2025, Version of Record 26 January 2025. https://doi.org/10.1016/j.neumar.2025.100036 Abstract Alzheimer's disease is a prevalent neurodegenerative disorder characterized by cognitive deficits and abnormal neurological activity. Recent evidence suggests that the pathogenesis of Alzheimer's disease may involve the abnormal expression of specific genes, particularly those associated with N6-methyladenosine modification. N6-methyladenosine is a common mRNA modification that influences mRNA splicing, translation, and stability, thereby regulating physiological processes and potentially contributing to neurodegenerative diseases. Our study aimed to identify and screen genes related to Alzheimer's disease, focusing on the METTL3 gene, a key regulator of m6A modification. We used a novel weighted metrics method that combines the METTL3 gene data with gene chip data from four stages of Alzheimer's disease samples through a Spearman-Cosine correlation weighing technique.By utilizing a correlation coefficient matrix strategy that integrates Spearman correlation and Pinched cosine correlation, we identified nine significantly differentially expressed genes associated with Alzheimer's disease. These genes, which are highly correlated with METTL3 during the transition from normal to disease states, suggest that m6A modification regulates METTL3 expression and affects the pathogenesis of Alzheimer's disease through multiple molecular pathways. Notably, our findings reveal a profound connection between m6A modification and energy metabolism, with observable effects on mitochondrial function, lipid metabolism, and glycolytic pathways. These genes, potentially serving as biomarkers, could advance the development of therapeutic strategies for Alzheimer's disease. Our results highlight the importance of m6A modification in Alzheimer's disease and suggest that the identified genes could be used as biomarkers for early detection and monitoring of the disease. The clinical significance of our findings lies in the potential to develop targeted therapies and improve patient outcomes by enhancing our understanding of the molecular mechanisms underlying Alzheimer's disease. 相关性分析确定与 N6-甲基腺苷修饰有关阿尔茨海默病相关基因可作为潜在生物标记物：一项回顾性观察性研究 摘要 阿尔茨海默病（Alzheimer's disease，AD）是一种常见的神经退行性疾病，以认知障碍和神经活动异常为特征。最近的证据表明，阿尔茨海默病的发病机制可能涉及特定基因的异常表达，尤其是那些与N6-甲基腺苷（m6A）修饰相关的基因。m6A是一种普遍的mRNA修饰，它影响mRNA的剪接、翻译和稳定性，从而调控生理过程，并可能导致神经退行性疾病。此研究旨在识别和筛选与阿尔茨海默病相关的基因，重点关注m6A修饰的关键调控因子METTL3基因。采用了一种新颖的Spearman 相关分析加权度量方法，将 METTL3 基因数据与来源于GEO数据库的 GSE1297数据集（包括7 例重度，8例中度，7例轻度阿尔茨海默病患者及9名正常对照）的基因芯片数据相结合。利用综合了斯皮尔曼相关性和夹余弦相关性的相关系数矩阵策略，确定了9个与阿尔茨海默病相关的显著差异表达基因。这些基因在从正常状态到疾病状态的转变过程中与 METTL3 高度相关，表明 m6A 修饰调节了这些基因的表达，并通过多种分子途径影响了阿尔茨海默病的发病机制。值得注意的是，此发现揭示了 m6A 修饰与能量代谢之间的深刻联系，对线粒体、脂质代谢和糖酵解途径都有明显的影响，这些基因有可能作为生物标志物，推动阿尔茨海默病治疗策略的开发。研究结果突出了m6A修饰在阿尔茨海默病中的重要性，并表明所发现的基因可作为生物标记物用于阿尔茨海默病的早期检测和监测。 |