β-amyloid and tau drive early Alzheimer's disease decline while glucose hypometabolism drives late decline
β-amyloid and tau drive early Alzheimer's disease decline while glucose hypometabolism drives late decline
复制标题
DOI：
10.1038/s42003-020-1079-x
复制
发表时间：
2020-07-06
影响因子：
5.9
通讯作者：
Lin, Ai-Ling
中科院分区：
文献类型：
--
作者：
Hammond, Tyler C.;Xing, Xin;Lin, Ai-Ling
在本文中，作者使用随机森林机器学习方法分析了阿尔茨海默病神经成像计划数据集，并确定A β和tau生物标志物是早期痴呆状态的更好预测因子，而葡萄糖代谢低下是晚期痴呆状态的更好预测因子。这些结果表明需要阶段导向的阿尔茨海默病治疗。临床试验集中在治疗候选人，修改β-淀粉样蛋白（A β）已多次失败治疗阿尔茨海默病（AD），这表明A β可能不是治疗AD的最佳靶点。已提出评估A β、tau和神经退行性（A/T/N）生物标志物用于AD分类。然而，目前尚不清楚是否在A/T/N框架的每一个臂的干扰在整个AD的进展同样的贡献。在这里，使用随机森林机器学习方法来分析阿尔茨海默病神经成像计划数据集中的参与者，我们表明A/T/N生物标志物在预测AD发展方面表现出不同的重要性，A β和tau的生物标志物升高更好地预测早期痴呆状态，神经退行性疾病的生物标志物，特别是葡萄糖代谢低下，更好地预测后期痴呆状态。我们的研究结果表明，AD治疗可能还需要以疾病阶段为导向，在早期AD中将A β和tau作为靶点，在晚期AD中将葡萄糖代谢作为靶点。
Here the authors analyze the Alzheimer's Disease Neuroimaging Initiative dataset using random forest machine learning methods and determine that A beta and tau biomarkers are better predictors of early dementia status, while glucose hypometabolism is a better predictor of later dementia status. These results suggest the need for stage-oriented Alzheimer's disease treatments.Clinical trials focusing on therapeutic candidates that modify beta-amyloid (A beta) have repeatedly failed to treat Alzheimer's disease (AD), suggesting that A beta may not be the optimal target for treating AD. The evaluation of A beta, tau, and neurodegenerative (A/T/N) biomarkers has been proposed for classifying AD. However, it remains unclear whether disturbances in each arm of the A/T/N framework contribute equally throughout the progression of AD. Here, using the random forest machine learning method to analyze participants in the Alzheimer's Disease Neuroimaging Initiative dataset, we show that A/T/N biomarkers show varying importance in predicting AD development, with elevated biomarkers of A beta and tau better predicting early dementia status, and biomarkers of neurodegeneration, especially glucose hypometabolism, better predicting later dementia status. Our results suggest that AD treatments may also need to be disease stage-oriented with A beta and tau as targets in early AD and glucose metabolism as a target in later AD.