Preserved Structural Network Organization Mediates Pathology Spread in Alzheimer's Disease Spectrum Despite Loss of White Matter Tract Integrity.
Preserved Structural Network Organization Mediates Pathology Spread in Alzheimer's Disease Spectrum Despite Loss of White Matter Tract Integrity.
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DOI：
10.3233/jad-170798
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
中科院分区：
文献类型：
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作者：
Powell F;Tosun D;Sadeghi R;Weiner M;Raj A;Alzheimer’s Disease Neuroimaging Initiative
阿尔茨海默病（AD）模型假设刻板进展通过白质（WM）纤维连接，最有可能通过沿神经元通路的毒性蛋白的跨突触传递。该领域的一个重要问题是纤维通路的组织是否以及如何受到疾病的影响。目前尚不清楚纤维是否作为退行性病理的导管，或者它们是否也与灰质网络一起退化。本研究在纵向设计中使用图论建模来研究WM网络组织对AD病理传播的影响。我们假设如果改变的WM网络组织介导疾病进展，那么先前发表的网络扩散模型将使用受试者特异性连接体代替健康模板连接体产生更高的预测精度。对124例ADNI患者的神经影像学资料进行评估。图拓扑度量显示，与对照组相比，患者中保留的网络组织。利用已发表的扩散模型，我们进一步探讨了网络改变对AD退化传播的影响。我们发现，连接体的选择对模型的预测能力没有显著影响。这些结果表明，尽管特定纤维束的完整性发生了可测量的变化，但AD中的WM网络组织仍然保持不变。此外，在健康和ad受损网络之间，假定的病理传播的中介没有差异。这一结论与先前报道AD的全局拓扑紊乱的结果有所不同。我们的数据表明，边缘阈值、二值化和皮层下区域包含到网络图的综合效应可能是先前报道的效应的原因。
Models of Alzheimer’s disease (AD) hypothesize stereotyped progression via white matter (WM) fiber connections, most likely via trans-synaptic transmission of toxic proteins along neuronal pathways. An important question in the field is whether and how organization of fiber pathways is affected by disease. It remains unknown whether fibers act as conduits of degenerative pathologies, or if they also degenerate with the gray matter network. This work uses graph theoretic modeling in a longitudinal design to investigate the impact of WM network organization on AD pathology spread. We hypothesize if altered WM network organization mediates disease progression, then a previously published network diffusion model will yield higher prediction accuracy using subject-specific connectomes in place of a healthy template connectome. Neuroimaging data in 124 subjects from ADNI were assessed. Graph topology metrics show preserved network organization in patients compared to controls. Using a published diffusion model, we further probe the effect of network alterations on degeneration spread in AD. We show that choice of connectome does not significantly impact the model’s predictive ability. These results suggest that, despite measurable changes in integrity of specific fiber tracts, WM network organization in AD is preserved. Further, there is no difference in the mediation of putative pathology spread between healthy and AD-impaired networks. This conclusion is somewhat at variance with previous results, which report global topological disturbances in AD. Our data indicates the combined effect of edge thresholding, binarization, and inclusion of subcortical regions to network graphs may be responsible for previously reported effects.