Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis.
Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis.
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DOI：
10.1038/ncomms11934
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发表时间：
2016-06-21
影响因子：
16.6
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
中科院分区：
文献类型：
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作者：
Iturria-Medina Y;Sotero RC;Toussaint PJ;Mateos-Pérez JM;Evans AC;Alzheimer’s Disease Neuroimaging Initiative
从综合的角度来看，迟发性阿尔茨海默病（LOAD）的多因素机制尚不清楚。研究表明，脑淀粉样蛋白-β沉积、代谢、血管、休息时功能活动、结构特性、认知完整性和外周蛋白水平的时空变化与LOAD进展有关。我们分析了来自阿尔茨海默病神经成像倡议（ADNI）的超过7700张脑图像和数十张血浆和脑脊液生物标志物。通过多因素数据驱动分析，我们获得了所有生物标志物的动态load异常指数，以及疾病进展的暂定时间顺序。影像学结果提示，脑内血管失调是疾病发展过程中的早期病理事件。认知能力下降在LOAD初始阶段是明显的，提示早期记忆缺陷与原发疾病因素有关。与血管系统完整性相关的特定蛋白质也观察到高异常水平。尽管仍然受到算法和所采用的生物标志物的敏感性的影响，我们的结果可能有助于预防性治疗干预措施的发展。迟发性阿尔茨海默病（LOAD）是一种复杂的多因素疾病。在这里，作者对LOAD进展进行了数据驱动分析，包括多模态脑成像、血浆和CSF生物标志物，并发现血管功能障碍是最早和最强的改变事件之一。
Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions. Late-onset Alzheimer's disease (LOAD) is a complex multi-factorial disorder. Here, the authors perform a data-driven analysis of LOAD progression, including multimodal brain imaging, plasma and CSF biomarkers, and find vascular dysfunction is among the earliest and strongest altered events.