Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
J Mol Neurosci. 2024 Apr 3;74(2):37. doi: 10.1007/s12031-024-02212-8.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory and cognitive impairment, often accompanied by alterations in mood, confusion, and, ultimately, a state of acute mental disturbance. The cerebral cortex is considered a promising area for investigating the underlying causes of AD by analyzing transcriptional patterns, which could be complemented by investigating blood samples obtained from patients. We analyzed the RNA expression profiles of three distinct areas of the brain cortex, including the frontal cortex (FC), temporal cortex (TC), and entorhinal cortex (EC) in patients with AD. Functional enrichment analysis was performed on the differentially expressed genes (DEGs) across the three regions. The two genes with the most significant expression changes in the EC region were selected for assessing mRNA expression levels in the peripheral blood of late-onset AD patients using quantitative PCR (qPCR). We identified eight shared DEGs in these regions, including AEBP1 and COLEC12, which exhibited prominent changes in expression. Functional enrichment analysis uncovered a significant association of these DEGs with the transforming growth factor-β (TGF-β) signaling pathway and processes related to angiogenesis. Importantly, we established a robust connection between the up-regulation of AEBP1 and COLEC12 in both the brain and peripheral blood. Furthermore, we have demonstrated the potential of AEBP1 and COLEC12 genes as effective diagnostic tools for distinguishing between late-onset AD patients and healthy controls. This study unveils the intricate interplay between AEBP1 and COLEC12 in AD and underscores their potential as markers for disease detection and monitoring.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是记忆和认知功能障碍，常伴有情绪改变、认知障碍，最终导致急性精神障碍。大脑皮层被认为是研究 AD 潜在原因的有希望的区域，通过分析转录模式，可以通过研究从患者获得的血液样本来补充。我们分析了 AD 患者三个不同大脑皮层区域（额叶皮层[FC]、颞叶皮层[TC]和内嗅皮层[EC]）的 RNA 表达谱。对三个区域的差异表达基因（DEG）进行了功能富集分析。选择 EC 区域中表达变化最显著的两个基因，使用定量 PCR（qPCR）评估迟发性 AD 患者外周血中的 mRNA 表达水平。我们在这些区域中鉴定出 8 个共同的 DEG，包括 AEBP1 和 COLEC12，它们的表达变化显著。功能富集分析揭示了这些 DEG 与转化生长因子-β（TGF-β）信号通路和与血管生成相关的过程之间存在显著关联。重要的是，我们在大脑和外周血中都建立了 AEBP1 和 COLEC12 的上调之间的稳健联系。此外，我们已经证明了 AEBP1 和 COLEC12 基因作为区分迟发性 AD 患者和健康对照的有效诊断工具的潜力。本研究揭示了 AD 中 AEBP1 和 COLEC12 之间的复杂相互作用，并强调了它们作为疾病检测和监测标志物的潜力。
