Each neurodegenerative syndrome reflects a stereotyped pattern of cellular, regional, and large-scale brain network degeneration. In behavioral variant of frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons (VENs), and fork cells are among the initial neuronal targets. These large layer 5 projection neurons are concentrated in the anterior cingulate and frontoinsular (FI) cortices, regions that anchor the salience network, a large-scale system linked to social-emotional function. Here, we studied patients with bvFTD, amyotrophic lateral sclerosis (ALS), or both, given that these syndromes share common pathobiological and genetic factors. Our goal was to determine how neuron type-specific TAR DNA-binding protein of 43 kDa (TDP-43) pathobiology relates to atrophy in specific brain structures and to loss of emotional empathy, a cardinal feature of bvFTD. We combined questionnaire-based empathy assessments, in vivo structural MR imaging, and quantitative histopathological data from 16 patients across the bvFTD/ALS spectrum. We show that TDP-43 pathobiology within right FI VENs and fork cells is associated with salience network atrophy spanning insular, medial frontal, and thalamic regions. Gray matter degeneration within these structures mediated loss of emotional empathy, suggesting a chain of influence linking the cellular, regional/network, and behavioral levels in producing signature bvFTD clinical features.

中文翻译：

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显着网络萎缩将神经元类型特异性病理学与额颞叶痴呆患者的同理心丧失联系起来。


每一种神经退行性综合症都反映了细胞、区域和大规模脑网络退化的刻板模式。在额颞叶痴呆 (bvFTD) 的行为变异型（一种社会情感功能障碍）中，冯·伊科诺莫神经元 (VEN) 和叉细胞是最初的神经元目标之一。这些大的第 5 层投射神经元集中在前扣带皮层和额岛皮层 (FI)，这些区域锚定显着网络，这是一个与社会情感功能相关的大型系统。在这里，我们研究了 bvFTD、肌萎缩侧索硬化症 (ALS) 或两者兼而有之的患者，因为这些综合征具有共同的病理生物学和遗传因素。我们的目标是确定神经元类型特异性 43 kDa TAR DNA 结合蛋白 (TDP-43) 病理学与特定大脑结构的萎缩和情感同理心丧失（bvFTD 的一个主要特征）之间的关系。我们结合了来自 16 名 bvFTD/ALS 谱系患者的基于问卷的共情评估、体内结构 MR 成像和定量组织病理学数据。我们发现右侧 FI VEN 和叉细胞内的 TDP-43 病理学与跨越岛叶、内侧额叶和丘脑区域的显着网络萎缩有关。这些结构内的灰质退化介导了情感同理心的丧失，这表明在产生标志性 bvFTD 临床特征时存在一系列连接细胞、区域/网络和行为水平的影响链。