通过综合性分析,ATP6V1E1和NDUFB5被确定为阿尔茨海默病的潜在生物标志物
Junjie Shao1, Xiuzhao Fan1, Shuangshuang Tian1
1Department of Nephrology, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
International journal of biological macromolecules
|November 16, 2025
概括
研究人员确定ATP6V1E1和NDUFB5是与阿尔茨海默病 (AD) 和线粒体功能障碍相关的关键基因. 这些基因被认为是阿尔茨海默病的早期诊断生物标志物,有助于及时干预策略.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 阿尔茨海默病 (AD) 是痴呆的主要原因.
- 线粒体功能障碍,特别是氧化酸化受损 (OXPHOS),是推动AD神经退行的一个关键特征.
- 识别早期生物标志物对于及时干预阿尔茨海默病至关重要.
研究的目的:
- 确定与OXPHOS相关的新生物标志物,用于早期检测阿尔茨海默病.
- 调查特定基因在阿尔茨海默氏症发病过程中的作用及其作为风险因素的潜力.
- 探索线粒体功能障碍,免疫细胞透和AD病理之间的联系.
主要方法:
- 来自AD叶和外周血液样本的差异表达基因的综合分析.
- 多变量逻辑回归和LASSO用于基因识别.
- 在独立的队列中验证,在AD小鼠模型中进行西部涂抹,并进行单细胞RNA-seq分析.
主要成果:
- ATP6V1E1和NDUFB5被确定为关键基因和潜在的AD风险因素,具有强大的诊断性能 (AUC>0.7).
- 这些基因在AD小鼠海马体中显著下调,并且与Aβ和Tau病理学负相关.
- 单细胞RNA-seq显示在微质中占主导表达,这表明与免疫失调和系统性OXPHOS损伤的联系.
结论:
- ATP6V1E1和NDUFB5是阿尔茨海默病的潜在早期指标.
- 这项研究揭示了AD病变发生过程中线粒体和 lysosomal 系统的协同功能障碍.
- 研究结果提供了对AD分子机制和潜在治疗策略的见解.
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