生物标志物 生物标志物
Julie Lee1, Balazs Toth1, Sandra Sanabria Bohorquez1
1Genentech, Inc., South San Francisco, CA, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 25, 2025
概括
研究人员在脑脊液 (CSF) 中发现了一种特定的,与阿尔茨海默氏症 (AD) 脑病理有很强的相关性. 这一发现提供了一个有希望的,可访问的生物标志物,用于在AD临床试验中评估tau纠.
科学领域:
- 神经科学是一个神经科学.
- 生物标志物发现发现
- 阿尔茨海默氏症疾病研究研究
背景情况:
- 由聚合的蛋白组成的神经纤维状结 (NFT) 是阿尔茨海默病 (AD) 的关键病理标志物.
- 在AD临床试验中,Tau是诊断,预后和评估治疗疗效的关键生物标志物.
- 目前通过PET扫描进行tau成像是由于成本和基础设施要求而受到限制的.
研究的目的:
- 研究特定脑脊液 (CSF) 溶解的tau物种与体内tau PET成像之间的相关性.
- 确定可访问的液体生物标志物作为PET成像的替代品,用于在AD临床试验中评估tau病理.
主要方法:
- 在53名AD参与者中使用DIA-MS,Elecsys,LC-MS和Simoa测定测量了CSF的tau物种 (总tau,pTau181,pTau205,N-term,中域,pTau217和蛋白质).
- 相关的CSF tau测量与[18F]GTP1 PET成像 (SUVR) 在皮质和超时区域.
- 在46个死后AD大脑中通过比较CSF和AT8阳性NFT负担在状回环中,验证了相关性.
主要成果:
- CSF pTau205,pTau217,以及来自2N4R异形MTBR区域的蛋白质,显示与[18F]GTP1 SUVR.的相关性最高.
- 该MTBR与状环中AT8阳性区域的百分比有很强的相关性,这表明大脑NFT负担.
结论:
- 来自TAU的MTBR区域的蛋白质性被确定为ADCSF中最高度相关的TAU物种,具有体内TAU PET成像和体外脑病理.
- 这种MTBR代表了一种潜在的液体生物标志物,用于评估AD中的tau病理,在临床试验中为PET成像提供了更容易获得的替代方案.
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