Antemortem network analysis of spreading pathology in autopsy-confirmed frontotemporal degeneration.
Antemortem network analysis of spreading pathology in autopsy-confirmed frontotemporal degeneration.
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DOI：
10.1093/braincomms/fcad147
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发表时间：
2023
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
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尽管在神经退行性疾病的动物模型中传播病理学的假设很清楚，但在人类中传播神经退行性病理学的基础一直难以确定。在这项研究中，我们使用图论分析的结构网络，在死前，多模态MRI尸检证实的情况下，检查散发性额颞叶变性的扩散病理。我们使用已发表的算法，在尸检的额颞叶变性与tau蛋白夹杂物或与transactional DNA结合蛋白的143 kDa夹杂物的T1加权MRI上定义进行性皮质萎缩的阶段。 我们研究了这些阶段中结构网络的全局和局部指数，重点关注灰质枢纽和枢纽之间投射的白色物质边缘的完整性。我们发现，与健康对照组相比，具有tau夹杂物的额颞叶变性和额颞叶变性-transformational DNA结合蛋白的43 kDa夹杂物的患者的全球网络措施受到同等程度的损害。 虽然局部网络完整性的措施都受到损害，在额颞叶变性与tau夹杂物和额颞叶变性transgeneral-transactional DNA结合蛋白的43 kDa夹杂物，我们发现了几个重要的特征，区分这些群体。 在对照组中识别的枢纽在两个患者组中均发生退化，但退化的枢纽仅在伴有tau蛋白夹杂物的额颞叶变性中与皮质萎缩的最早期（即epicentres）相关。在额颞叶变性与tau内含物中，退化边缘比在额颞叶变性-transactional DNA结合蛋白中的43 kDa内含物中显著更丰富，这表明tau病理学的传播涉及更显著的白色物质变性。 在额颞叶变性与tau夹杂物中，弱化的边缘与退化的枢纽相关联，而在额颞叶变性与tau夹杂物的DNA结合蛋白中，尤其是在疾病的早期阶段，特别是在疾病的早期阶段，并且在额颞叶变性与tau夹杂物中的阶段到阶段的转变的特征在于在疾病的后续阶段中，在早期阶段中的弱化的边缘投射到患病的枢纽。 当我们检查病理从早期患病的区域到后续阶段的物理相邻区域的传播时，我们发现在额颞叶变性中有更多证据表明疾病传播到相邻区域- 我们将退化的灰质枢纽和弱化的白色物质边缘的证据与直接观察患者大脑样本的数字化病理学定量测量相关联。我们从这些观察结果得出结论，病理从患病区域通过弱化的长程边缘传播到远处区域可能有助于额颞叶痴呆-tau的疾病传播，而病理通过局部神经元连接传播到物理相邻区域可能在额颞叶变性-transactional DNA结合蛋白的43 kDa内含物的疾病传播中发挥更突出的作用。 Chen等人利用死前多模式MRI的图论分析来检查尸检证实的额颞叶变性患者的结构网络中的扩散病理学，这些变性伴tau蛋白或transactional DNA结合蛋白（约43 kDa内含物）。 他们报告了这两种病理之间的远程和短程网络退化的不同模式，表明它们的传播机制不同。
Despite well-articulated hypotheses of spreading pathology in animal models of neurodegenerative disease, the basis for spreading neurodegenerative pathology in humans has been difficult to ascertain. In this study, we used graph theoretic analyses of structural networks in antemortem, multimodal MRI from autopsy-confirmed cases to examine spreading pathology in sporadic frontotemporal lobar degeneration. We defined phases of progressive cortical atrophy on T1-weighted MRI using a published algorithm in autopsied frontotemporal lobar degeneration with tau inclusions or with transactional DNA binding protein of ∼43 kDa inclusions. We studied global and local indices of structural networks in each of these phases, focusing on the integrity of grey matter hubs and white matter edges projecting between hubs. We found that global network measures are compromised to an equal degree in patients with frontotemporal lobar degeneration with tau inclusions and frontotemporal lobar degeneration-transactional DNA binding protein of ∼43 kDa inclusions compared to healthy controls. While measures of local network integrity were compromised in both frontotemporal lobar degeneration with tau inclusions and frontotemporal lobar degeneration-transactional DNA binding protein of ∼43 kDa inclusions, we discovered several important characteristics that distinguished between these groups. Hubs identified in controls were degraded in both patient groups, but degraded hubs were associated with the earliest phase of cortical atrophy (i.e. epicentres) only in frontotemporal lobar degeneration with tau inclusions. Degraded edges were significantly more plentiful in frontotemporal lobar degeneration with tau inclusions than in frontotemporal lobar degeneration-transactional DNA binding protein of ∼43 kDa inclusions, suggesting that the spread of tau pathology involves more significant white matter degeneration. Weakened edges were associated with degraded hubs in frontotemporal lobar degeneration with tau inclusions more than in frontotemporal lobar degeneration-transactional DNA binding protein of ∼43 kDa inclusions, particularly in the earlier phases of the disease, and phase-to-phase transitions in frontotemporal lobar degeneration with tau inclusions were characterized by weakened edges in earlier phases projecting to diseased hubs in subsequent phases of the disease. When we examined the spread of pathology from a region diseased in an earlier phase to physically adjacent regions in subsequent phases, we found greater evidence of disease spreading to adjacent regions in frontotemporal lobar degeneration-transactional DNA binding protein of ∼43 kDa inclusions than in frontotemporal lobar degeneration with tau inclusions. We associated evidence of degraded grey matter hubs and weakened white matter edges with quantitative measures of digitized pathology from direct observations of patients’ brain samples. We conclude from these observations that the spread of pathology from diseased regions to distant regions via weakened long-range edges may contribute to spreading disease in frontotemporal dementia-tau, while spread of pathology to physically adjacent regions via local neuronal connectivity may play a more prominent role in spreading disease in frontotemporal lobar degeneration-transactional DNA binding protein of ∼43 kDa inclusions. Chen et al. utilize graph-theoretic analyses of antemortem, multimodal MRIs to examine spreading pathology in structural networks of those with autopsy-confirmed frontotemporal lobar degeneration with either tau or transactional DNA binding protein of ∼43 kDa inclusions. They report distinct patterns of long-range and short-range network degradation between the two pathologies, suggesting different mechanisms for their spread.
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影响因子：
9.9
作者：
Abrahams, S;Leigh, PN;Goldstein, LH
通讯作者：
Goldstein, LH
影响因子：
7.1
作者：
Giannini LAA;Peterson C;Ohm D;Xie SX;McMillan CT;Raskovsky K;Massimo L;Suh E;Van Deerlin VM;Wolk DA;Trojanowski JQ;Lee EB;Grossman M;Irwin DJ
通讯作者：
Irwin DJ
影响因子：
6
作者：
Forman, MS;Zhukareva, V;Trojanowski, JQ
通讯作者：
Trojanowski, JQ
影响因子：
4.2
作者：
Agosta, Federica;Galantucci, Sebastiano;Filippi, Massimo
通讯作者：
Filippi, Massimo
DOI：
10.1093/brain/awu132
发表时间：
2014-08
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Crossley NA;Mechelli A;Scott J;Carletti F;Fox PT;McGuire P;Bullmore ET
通讯作者：
Bullmore ET