生物标志物 生物标志物
Linda Karlsson1, Shorena Janelidze1, Nicolas R Barthélemy2
1Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Lund, Sweden.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 24, 2025
概括
将阿尔茨海默病 (AD) 液体生物标志物与参考蛋白质如Aβ40或非酸化 (np-tau) 进行正常化,显著改善了它们与大脑粉样蛋白和病理学的关联. 这提高了脑脊液 (CSF) 和血AD生物标志物的精度.
科学领域:
- 生物标志物的发现和验证.
- 神经退行性疾病诊断神经退行性疾病诊断
- 阿尔茨海默病 (AD) 研究研究
背景情况:
- 液体生物标志物对于阿尔茨海默病 (AD) 检测具有成本效益,但个体间的变化可能会影响准确性.
- 之前的工作确定了参考蛋白质,改善了CSF Aβ42 / PET和CSF p-tau181 / PET之间的一致性.
- 参考蛋白对CSFAD生物标志物与大脑病理学和血生物标志物改善相关性的影响尚不清楚.
研究的目的:
- 为了研究参考蛋白对脑脊液 (CSF) AD生物标志物与大脑/粉样蛋白-β (Aβ) PET负载之间的关系的影响.
- 为了确定血AD生物标志物是否可以通过结合参考蛋白来改善.
- 评估使用CSF Aβ40或非化 (np-tau) 对生物标志物-病理学关联的正常化影响.
主要方法:
- 使用瑞典BioFINDER-2队列 (n=1702) 进行分析.
- 单独比较tau/Aβ-PET负载和CSF生物标志物 (例如,MTBR-tau243,p-tau异型,SNAP-25) 与使用单变量线性回归进行对参考蛋白 (Aβ40,np-tau) 的规范化之间的关联.
- 将分析扩展到血生物标志物,并在骑士ADRC和TRIAD队列中验证了发现.
主要成果:
- 脑脊髓细胞Aβ40的正常化显著加强了脑脊髓细胞生物标志物 (MTBR-tau243,p-tau异型,突触生物标志物) 和tau/Aβ-PET之间的关联.
- 对CSF np-tau的规范化主要改善了CSF生物标志物和Aβ-PET之间的一致性.
- 血生物标志物与tau/Aβ-PET的关联通过与血Aβ40或np-tau的正常化得到增强,研究结果在队列中复制.
结论:
- 对参考蛋白 (Aβ40或np-tau) 的规范化增强了CSF和血AD生物标志物与大脑tau和Aβ病理学之间的关联.
- 这种规范化策略提高了已建立的AD和突触液生物标志物的精度.
- 参考蛋白正常化提高了阿尔茨海默病的液体生物标志物的准确性和可解释性.
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