论文标题
在阿尔茨海默氏病的动态神经病理事件下，发现人脑的脆弱性和临界性
Uncovering the System Vulnerability and Criticality of Human Brain under Dynamical Neuropathological Events in Alzheimer's Disease
论文作者
论文摘要
背景：尽管在研究淀粉样蛋白 - \ b {eta}（a），蛋白质tau（t）和神经变性（[n]）生物标志物背后的神经生物学因素方面做出了巨大努力，但在[n]生物标记物中如何散布在整个大脑中的机制途径，但如何流行。目的：消除广告进展中的巨大异质性，并确定脆弱/关键的大脑区域对AD病理学。方法：在这项工作中，我们使用了一种新型的双态反应扩散模型来表征AT [N]生物标志物及其在大脑网络之间的传播的相互作用，这使我们能够建立对阿尔茨海默氏病（AD）进展的新系统生物学的基础。我们将模型应用于ADNI数据库的大规模纵向神经图像，并研究了大脑的系统脆弱性和批判性。结果：我们的模型产生的长期预测具有统计学意义的线性与时间成像数据相关，产生临床一致的风险预测，并捕获了[N]生物标志物在AD开发中的Braak样扩散模式。结论：我们的主要发现包括（i）tau是与淀粉样蛋白相比的区域风险更强的指标，（ii）颞叶表现出更高的与广告相关病理的脆弱性，（iii）提出的关键大脑区域优于整个大脑的疾病和（iv）在整个大脑中的疾病中的临界大脑nodes，以及（IV），以及（iv），（iv）ex e e e e e e e e e e e e e e e e e e e e e eta nove by node node node node node node node node node node node。扩散，代谢平衡的破坏是导致阿尔茨海默氏病启动和发展的最决定因素。
Background: Despite the striking efforts in investigating neurobiological factors behind the acquisition of amyloid-\b{eta} (A), protein tau (T), and neurodegeneration ([N]) biomarkers, the mechanistic pathways of how AT[N] biomarkers spreading throughout the brain remain elusive. Objectives: To disentangle the massive heterogeneities in AD progressions and identify vulnerable/critical brain regions to AD pathology. Methods: In this work, we characterized the interaction of AT[N] biomarkers and their propagation across brain networks using a novel bistable reaction-diffusion model, which allows us to establish a new systems biology underpinning of Alzheimer's disease (AD) progression. We applied our model to large-scale longitudinal neuroimages from the ADNI database and studied the systematic vulnerability and criticality of brains. Results: Our model yields long term prediction that is statistically significant linear correlated with temporal imaging data, produces clinically consistent risk prediction, and captures the Braak-like spreading pattern of AT[N] biomarkers in AD development. Conclusion: Our major findings include (i) tau is a stronger indicator of regional risk compared to amyloid, (ii) temporal lobe exhibits higher vulnerability to AD-related pathologies, (iii) proposed critical brain regions outperform hub nodes in transmitting disease factors across the brain, and (iv) comparing the spread of neuropathological burdens caused by amyloid-\b{eta} and tau diffusions, disruption of metabolic balance is the most determinant factor contributing to the initiation and progression of Alzheimer's disease.
