生物标志物 生物标志物
Bart Smets1, Asif Emon2, Yanfei Zhang3
1Janssen Pharmaceutica NV, a Johnson & Johnson company, Beerse, Belgium.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 26, 2025
概括
阿尔茨海默病 (AD) 除了粉样蛋白和病理之外,还具有不同的分子亚型. 使用CSF蛋白质组学识别这些亚型可以改善AD患者的诊断和治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 生物标志物 生物标志物
- 蛋白质组学是指蛋白质组学.
背景情况:
- 根据A/T/N框架,阿尔茨海默病 (AD) 根据粉样斑块 (A) 和团 (T) 进行分类,通过液体和成像生物标志物进行早期诊断.
- 然而,A/T/N框架并不涵盖所有AD的发病途径,因为共同病理显著影响疾病的进展和治疗反应.
研究的目的:
- 通过使用脑脊液 (CSF) 蛋白质学来识别不同的患者亚组,研究阿尔茨海默病 (AD) 中的分子异质性.
- 为了比较已识别的AD亚型的临床,遗传和分子特征,并评估它们与疾病阶段的关系.
- 使用血蛋白学开发CSF亚型的预测模型.
主要方法:
- 在西班牙ACE队列中分析了来自705个CSF粉样蛋白水平异常的人的CSF蛋白质组数据.
- 应用共识聚类来识别AD患者的分子亚型.
- XGBoost分类器受过训练,可以从血蛋白质组学数据中预测CSF亚型.
主要成果:
- 确定两个强大的CSF亚型: (1) 神经元可塑性高,CSFp-tau181和t-tau升高,以及 (2) 血脑屏障功能障碍,涉及补充,炎症和凝血通路.
- 在神经元损伤标志物或疾病进展率上没有观察到显著差异,这表明分子异质性而不是疾病阶段差异.
- 基因分析揭示了亚型的不同潜在病因,表明需要量身定制的治疗模式. 血蛋白质学准确地预测了CSF亚型 (AUC> 0.8).
结论:
- 这项研究证实了AD的独特分子亚型,该亚型使患者的分层超出了A/T/N分类.
- 在额外的队列和临床试验中进一步验证对于提高AD诊断,预后和治疗的精度至关重要.
- 针对这些亚型的基于血液的生物标志物的开发将在阿尔茨海默病研究中显著推进个性化医学方法.
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