揭示阿尔茨海默病动态神经病理事件下人脑的系统脆弱性与临界性
Uncovering the System Vulnerability and Criticality of Human Brain under Dynamical Neuropathological Events in Alzheimer's Disease
AI总结：
提出双稳态反应-扩散模型刻画AT[N]生物标志物在脑网络中的相互作用与传播，并基于ADNI纵向影像识别人脑脆弱及关键区域。
摘要：
背景：尽管在研究淀粉样蛋白-β（A）、tau蛋白（T）和神经退行性变（[N]）生物标志物获得背后的神经生物学因素方面付出了显著努力，但AT[N]生物标志物如何在全脑扩散的机制路径仍不清楚。目标：厘清阿尔茨海默病（AD）进展中的巨大异质性，并识别对AD病理脆弱或关键的脑区。方法：在本研究中，我们使用一种新型双稳态反应-扩散模型刻画了AT[N]生物标志物的相互作用及其在脑网络中的传播，这使我们能够建立阿尔茨海默病进展的新系统生物学基础。我们将模型应用于ADNI数据库的大规模纵向神经影像，研究了脑的系统性脆弱性和临界性。结果：我们的模型给出的长期预测与时序影像数据具有统计显著的线性相关，产生了与临床一致的风险预测，并捕捉到AD发展中AT[N]生物标志物类似Braak分期的扩散模式。结论：主要发现包括：（i）与淀粉样蛋白相比，tau是更强的区域风险指标；（ii）颞叶对AD相关病理表现出更高脆弱性；（iii）所提出的关键脑区在全脑传递疾病因子方面优于枢纽节点；（iv）比较淀粉样蛋白-β和tau扩散导致的神经病理负荷传播后，代谢平衡破坏是促成阿尔茨海默病发生和进展最具决定性的因素。
英文摘要：
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.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
