Amygdala TDP-43 Pathology in Frontotemporal Lobar Degeneration and Motor Neuron Disease
Amygdala TDP-43 Pathology in Frontotemporal Lobar Degeneration and Motor Neuron Disease
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杏仁核 TDP-43 额颞叶变性和运动神经元疾病的病理学
DOI：
10.1093/jnen/nlx063
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发表时间：
2017
影响因子：
3.2
通讯作者：
Duyckaerts Charles
中科院分区：
文献类型：
--
作者：
Takeda Takahiro;Seilhean Danielle;Le Ber Isabelle;Millecamps Stephanie;Sazdovitch Veronique;Kitagawa Kazuo;Uchihara Toshiki;Duyckaerts Charles
TDP-43阳性包涵体存在于额颞叶变性（FTLD）和运动神经元疾病（MND）（包括肌萎缩侧索硬化症）的杏仁核中。行为异常是FTLD的主要症状之一，可能至少部分与杏仁核病理有关。我们检测了散发性FTLD/MND（sFTLD/MND）、FTLD/MND伴C9 ORF 72突变（FTLD/MND-C9）和FTLD伴颗粒蛋白前体突变（FTLD-GRN）患者杏仁核中TDP-43包涵体。TDP-43夹杂物在这些亚型中的每一个中是常见的，否则可以在地形和遗传基础上进行区分。进行常规和免疫染色，我们量化的区域基础上的夹杂物的数密度。26例sFTLD/MND中10例、9例FTLD/MND-C9中5例、4例FTLD-GRN中均可见杏仁核内TDP-43包涵体。在FTLD/MND-C9中，它们的数密度低于sFTLD/MND和FTLD-GRN。TDP-43包涵体在所有亚型的基底外侧核组的腹侧区域中较多。这种对比在散发性和C9突变的FTLD/MND中是明显的，而在FTLD-GRN中不太明显。杏仁核分区参与的这种差异可能与FTLD/MND和FTLD-GRN中不同影响的区域特异性神经元连接有关。
TDP-43-positive inclusions are present in the amygdala in frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND) including amyotrophic lateral sclerosis. Behavioral abnormalities, one of the chief symptoms of FTLD, could be, at least partly, related to amygdala pathology. We examined TDP-43 inclusions in the amygdala of patients with sporadic FTLD/MND (sFTLD/MND), FTLD/MND with mutation of theC9ORF72(FTLD/MND-C9) and FTLD with mutation of the progranulin (FTLD-GRN). TDP-43 inclusions were common in each one of these subtypes, which can otherwise be distinguished on topographical and genetic grounds. Conventional and immunological stainings were performed and we quantified the numerical density of inclusions on a regional basis. TDP-43 inclusions in amygdala could be seen in 10 out of 26 sFTLD/MND cases, 5 out of 9 FTLD/MND-C9 cases, and all 4 FTLD-GRN cases. Their numerical density was lower in FTLD/MND-C9 than in sFTLD/MND and FTLD-GRN. TDP-43 inclusions were more numerous in the ventral region of the basolateral nucleus group in all subtypes. This contrast was apparent in sporadic and C9-mutated FTLD/MND, while it was less evident in FTLD-GRN. Such differences in subregional involvement of amygdala may be related to the region-specific neuronal connections that are differentially affected in FTLD/MND and FTLD-GRN.