Zhao Yejing, Wang Xiang, Zhang Jie, Zhao Yanyan, Li Yi, Shen Ji, Yuan Ying, Li Jing
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Department of Geriatrics, Institute of Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, China.
Front Neurosci. 2025 Aug 26;19:1663276. doi: 10.3389/fnins.2025.1663276. eCollection 2025.
The contemporary consensus firmly emphasizes the urgent need to reorient research efforts toward the early detection of preclinical Alzheimer's disease (AD) or mild cognitive impairment (MCI). However, there is still a notable absence of novel biomarkers that are both efficient, minimally invasive, and cost-effective in real-world clinical settings. To address this gap, datasets GSE29378 and GSE12685 were selected to screen differentially expressed genes (DEGs), and hub genes were identified by different algorithms. A total of 350 DEGs were identified in bioinformatics data mining. Functional enrichment analysis showed that fibroblast growth factor 2(FGF2) and yes-associated protein 1(YAP1) protein levels were highly expressed in AD samples, indicating their potential regulatory roles in AD. Between October and November 2024, a total of 146 elderly individuals diagnosed with MCI and 54 healthy elderly subjects were successfully recruited. Enzyme linked immunosorbent assay (ELISA) was used to detect plasma hub gene protein concentration. The results showed that the expression levels of plasma FGF2 and YAP1 proteins in the MCI group were significantly higher compared to the control group. Logistic regression analysis indicated that high plasma FGF2 and YAP1 expression levels were independently associated with MCI in the elderly. The Area under the curve (AUC) of FGF2 model and YAP1 model were 0.907 and 0.972, respectively. Therefore, the high expression of plasma FGF2 and YAP1 proteins may be independent predictive risk factors for MCI in the elderly. Our findings may provide targets for the development of early minimally invasive, efficient, and convenient screening tools, and even for the treatment of AD in the future.
当代共识坚定地强调迫切需要将研究工作重新导向临床前阿尔茨海默病（AD）或轻度认知障碍（MCI）的早期检测。然而，在现实世界的临床环境中，仍然明显缺乏既高效、微创又具有成本效益的新型生物标志物。为了填补这一空白，选择了数据集GSE29378和GSE12685来筛选差异表达基因（DEG），并通过不同算法鉴定枢纽基因。在生物信息学数据挖掘中总共鉴定出350个DEG。功能富集分析表明，成纤维细胞生长因子2（FGF2）和Yes相关蛋白1（YAP1）蛋白水平在AD样本中高表达，表明它们在AD中具有潜在的调节作用。在2024年10月至11月期间，成功招募了146名被诊断为MCI的老年人和54名健康老年受试者。采用酶联免疫吸附测定（ELISA）检测血浆枢纽基因蛋白浓度。结果显示，MCI组血浆FGF2和YAP1蛋白的表达水平明显高于对照组。逻辑回归分析表明，血浆FGF2和YAP1高表达水平与老年人MCI独立相关。FGF2模型和YAP1模型的曲线下面积（AUC）分别为0.907和0.972。因此，血浆FGF2和YAP1蛋白的高表达可能是老年人MCI的独立预测危险因素。我们的研究结果可能为开发早期微创、高效且便捷的筛查工具甚至未来AD的治疗提供靶点。
