揭示脑网络结构与功能连接如何分区域影响阿尔茨海默病中淀粉样蛋白扩散。
Understanding Mechanistic Role of Structural and Functional Connectivity in Tau Propagation Through Multi-Layer Modeling
- 构建多层图扩散模型，分析结构与功能连接的交互作用。
- 功能连接主导早期病变，结构连接在晚期起主要作用。
- 结果与炎症、细胞凋亡相关基因表达高度吻合，适合神经科学与临床研究者。
新兴神经影像学证据表明，病理态的tau蛋白沿特定脑网络积累，提示大规模网络架构在阿尔茨海默病（AD）进展中起关键作用。然而，结构连接（SC）与功能连接（FC）如何相互作用影响tau传播仍不明确。基于前所未有的纵向神经影像数据，我们通过多层图扩散模型探究了SC-FC的交互作用。结果不仅显示脑连接组架构限制了tau传播，还揭示了区域性的不对称贡献：在皮层下区域、岛叶、额叶和颞叶，FC主导tau传播；而在枕叶、顶叶和边缘系统，SC作用更大。随着疾病进展，SC与FC的主导地位发生转变，早期以FC为主，晚期则转为SC主导。SC与FC主导区域的空间分布与涉及炎症、凋亡及溶酶体功能的阿尔茨海默病相关基因（如CHUK、TMEM106B、MCL1、NOTCH1、TH）的区域表达高度一致。此外，不可变风险因素（如APOE基因型、性别）和生物学机制（如淀粉样蛋白沉积）通过区域性地重塑传播路径，改变解剖与功能通路的主导关系。研究结果在独立队列中得到验证。
原文摘要 · Abstract (English)
Emerging neuroimaging evidence shows that pathological tau proteins build up along specific brain networks, suggesting that large-scale network architecture plays a key role in the progression of Alzheimer's disease (AD). However, how structural connectivity (SC) and functional connectivity (FC) interact to influence tau propagation remains unclear. Leveraging an unprecedented volume of longitudinal neuroimaging data, we examine SC-FC interactions through a multi-layer graph diffusion model. Beyond showing that connectome architecture constrains tau spread, our model reveals a regionally asymmetric contribution of SC and FC. Specifically, FC predominantly drives tau spread in subcortical areas, the insula, frontal and temporal cortices, whereas SC plays a larger role in occipital, parietal, and limbic regions. The relative dominance of SC versus FC shifts over the course of disease, with FC generally prevailing in early AD and SC becoming primary in later stages. Spatial patterns of SC- and FC-dominant regions strongly align with the regional expression of AD-associated genes involved in inflammation, apoptosis, and lysosomal function, including CHUK (IKK-alpha), TMEM106B, MCL1, NOTCH1, and TH. In parallel, other non-modifiable risk factors (e.g., APOE genotype, sex) and biological mechanisms (e.g., amyloid deposition) selectively reshape tau propagation by shifting dominant routes between anatomical and functional pathways in a region-specific manner. Findings are validated in an independent AD cohort.
Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品；中文卡片由大模型生成，请以原文为准。