Neuroanatomical and cellular degeneration associated with a social disorder characterized by new ritualistic belief systems in a TDP-C patient vs. a Pick patient.
Neuroanatomical and cellular degeneration associated with a social disorder characterized by new ritualistic belief systems in a TDP-C patient vs. a Pick patient.
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DOI：
10.3389/fneur.2023.1245886
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发表时间：
2023
影响因子：
3.4
通讯作者：
中科院分区：
文献类型：
--
作者：
额颞性痴呆(FTD)是临床和病理上异质性神经退行性痴呆的一种表现。FTD的临床和解剖变异已被描述，并与潜在的额颞叶变性(FTLD)病理有关，包括tauopathies(FTLD-tau)或TDP-43蛋白病变(FTLD-TDP)。以前颞叶皮质变性为主的FTD患者常出现语义知识缺失的语言障碍和/或社会障碍，其特征分别为左右半球受累对应的强迫性仪式和信仰系统。这些复杂的社会障碍的神经基础仍不清楚。在这里，我们提供了两名患者的对比成像和尸检研究，一名患者患有FTLD-TDP(C亚型)，另一名患者患有FTLD-tau(Pick病亚型)，他们都形成了新的僵化信念体系。FTLD-TDP患者形成了一套复杂的价值观，以积极为中心，并与猪的特定身体和行为特征相关联，而FTLD-tau患者则发展出与积极和灵性的一般主题相关的强制性、目标导向行为。神经影像显示FTLD-TDP患者以左侧为主的颞叶萎缩，FTLD-tau患者以右侧为主的额颞叶萎缩。与生前皮质萎缩一致，组织病理学检查显示两名患者主要在前颞叶有严重的神经元和髓鞘丢失，但FTLD-tau患者表现为更多的双侧背外侧受累，表现为更严重的病理改变，投射神经元和深部白质的丢失。这些发现突显出，前颞叶内和与之相连的区域可能对不同的FTLD蛋白病变具有不同的易感性，并在人类信念系统中发挥重要作用。
Frontotemporal dementia (FTD) is a spectrum of clinically and pathologically heterogenous neurodegenerative dementias. Clinical and anatomical variants of FTD have been described and associated with underlying frontotemporal lobar degeneration (FTLD) pathology, including tauopathies (FTLD-tau) or TDP-43 proteinopathies (FTLD-TDP). FTD patients with predominant degeneration of anterior temporal cortices often develop a language disorder of semantic knowledge loss and/or a social disorder often characterized by compulsive rituals and belief systems corresponding to predominant left or right hemisphere involvement, respectively. The neural substrates of these complex social disorders remain unclear. Here, we present a comparative imaging and postmortem study of two patients, one with FTLD-TDP (subtype C) and one with FTLD-tau (subtype Pick disease), who both developed new rigid belief systems. The FTLD-TDP patient developed a complex set of values centered on positivity and associated with specific physical and behavioral features of pigs, while the FTLD-tau patient developed compulsive, goal-directed behaviors related to general themes of positivity and spirituality. Neuroimaging showed left-predominant temporal atrophy in the FTLD-TDP patient and right-predominant frontotemporal atrophy in the FTLD-tau patient. Consistent with antemortem cortical atrophy, histopathologic examinations revealed severe loss of neurons and myelin predominantly in the anterior temporal lobes of both patients, but the FTLD-tau patient showed more bilateral, dorsolateral involvement featuring greater pathology and loss of projection neurons and deep white matter. These findings highlight that the regions within and connected to anterior temporal lobes may have differential vulnerability to distinct FTLD proteinopathies and serve important roles in human belief systems.
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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：
38.1
作者：
Grossman, Murray
通讯作者：
Grossman, Murray
影响因子：
5.3
作者：
Baker, Arielle;Kalmbach, Brian;Dembrow, Nikolai
通讯作者：
Dembrow, Nikolai
影响因子：
14.5
作者：
Bevan-Jones, W. Richard;Cope, Thomas E.;Rowe, James B.
通讯作者：
Rowe, James B.
影响因子：
8.2
作者：
Godefroy，Valerie;Sezer，Idil;Migliaccio，Raffaella
通讯作者：
Migliaccio，Raffaella