Corticobasal degeneration with TDP-43 pathology presenting with progressive supranuclear palsy syndrome: a distinct clinicopathologic subtype.
Corticobasal degeneration with TDP-43 pathology presenting with progressive supranuclear palsy syndrome: a distinct clinicopathologic subtype.
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皮质基底节变性伴 TDP-43 病理，表现为进行性核上性麻痹综合征：一种独特的临床病理亚型。
DOI：
10.1007/s00401-018-1878-z
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发表时间：
2018-09
影响因子：
12.7
通讯作者：
Dickson DW
中科院分区：
文献类型：
--
作者：
Koga S;Kouri N;Walton RL;Ebbert MTW;Josephs KA;Litvan I;Graff-Radford N;Ahlskog JE;Uitti RJ;van Gerpen JA;Boeve BF;Parks A;Ross OA;Dickson DW
皮质基底节变性（CBD）是一种临床异质性tau蛋白病，与进行性核上性麻痹（PSP）具有重叠的临床病理和遗传特征。本研究旨在阐明是否反式反应DNA结合蛋白43 kDa（TDP-43）病理有助于CBD的临床病理异质性。石蜡包埋切片的中脑，脑桥，丘脑底核，基底前脑从尸检证实的CBD案件进行了筛选与磷酸TDP-43的免疫组织化学。在TDP-43病理学病例中，对其他脑区（即中央前回、扣带回和上级额回、海马、髓质和小脑）进行免疫染色。根据TDP-43病理的局部分布和严重程度进行系统聚类分析，并比较聚类之间的临床病理和遗传特征。在45%的CBD病例中观察到TDP-43病理学，最常见于中脑被盖（TDP-43阳性病例的80%），其次是丘脑底核（69%）。系统聚类分析将TDP-43阳性的CBD分为TDP限制型（52%）和TDP重度型（48%）。与TDP限制型和TDP阴性患者相比，TDP重度患者更可能被临床诊断为PSP（80% vs 32% vs 30%，P <0.001）。向下凝视麻痹的存在是PSP生前诊断的最强因素，中脑顶盖中的严重TDP-43病理与向下凝视麻痹密切相关。此外，在橄榄脑桥小脑系统中的tau负荷在TDP阳性的CBD中显著大于TDP阴性的CBD。遗传分析显示，MAPT H1/H1基因型频率在严重TDP中显著低于TDP阴性和TDP限制性CBD（65% vs 89% vs 91%，p <0.001）。GRN rs 5848和TMEM 106 B rs3173615的纯合次要等位基因频率在三组之间没有显著差异。总之，本研究表明，CBD与严重的TDP-43病理是一个独特的临床病理亚型的CBD，其特征是PSP样的临床表现，严重的tau病理在橄榄脑桥小脑系统，和低频率的MAPT H1单倍型。
Corticobasal degeneration (CBD) is a clinically heterogeneous tauopathy, which has overlapping clinicopathologic and genetic characteristics with progressive supranuclear palsy (PSP). This study aimed to elucidate whether transactive response DNA-binding protein of 43 kDa (TDP-43) pathology contributes to clinicopathologic heterogeneity of CBD. Paraffin-embedded sections of the midbrain, pons, subthalamic nucleus, and basal forebrain from autopsy-confirmed CBD cases were screened with immunohistochemistry for phospho-TDP-43. In cases with TDP-43 pathology, additional brain regions (i.e. precentral, cingulate, and superior frontal gyri, hippocampus, medulla, and cerebellum) were immunostained. Hierarchical clustering analysis was performed based on the topographical distribution and severity of TDP-43 pathology, and clinicopathologic and genetic features were compared between the clusters. TDP-43 pathology was observed in 45% of CBD cases, most frequently in midbrain tegmentum (80% of TDP-43-positive cases), followed by subthalamic nucleus (69%). TDP-43-positive CBD was divided into TDP-limited (52%) and TDP-severe (48%) by hierarchical clustering analysis. TDP-severe patients were more likely to have been diagnosed clinically as PSP compared to TDP-limited and TDP-negative patients (80% vs 32% vs 30%, P <0.001). Presence of downward gaze palsy was the strongest factor for the antemortem diagnosis of PSP, and severe TDP-43 pathology in the midbrain tectum was strongly associated with downward gaze palsy. In addition, tau burden in the olivopontocerebellar system was significantly greater in TDP-positive than TDP-negative CBD. Genetic analyses revealed that MAPT H1/H1 genotype frequency was significantly lower in TDP-severe than in TDP-negative and TDP-limited CBD (65% vs 89% vs 91%, p <0.001). The homozygous minor allele frequencies in GRN rs5848 and TMEM106B rs3173615 were not significantly different between the three groups. In conclusion, the present study indicates that CBD with severe TDP-43 pathology is a distinct clinicopathologic subtype of CBD, characterized by PSP-like clinical presentations, severe tau pathology in the olivopontocerebellar system, and low frequency of MAPT H1 haplotype.
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对医疗统计信息的自由使用的易于使用的软件“ EZR”的调查。
影响因子：
4.8
作者：
Kanda Y
通讯作者：
Kanda Y
影响因子：
5
作者：
Koga S;Lin WL;Walton RL;Ross OA;Dickson DW
通讯作者：
Dickson DW
影响因子：
3.5
作者：
Baker, M;Litvan, I;Hutton, M
通讯作者：
Hutton, M
DOI：
10.1002/mds.27198
发表时间：
2017-12
期刊：
Movement disorders : official journal of the Movement Disorder Society
影响因子：
--
作者：
Koga S;Parks A;Kasanuki K;Sanchez-Contreras M;Baker MC;Josephs KA;Ahlskog JE;Uitti RJ;Graff-Radford N;van Gerpen JA;Wszolek ZK;Rademakers R;Dickson DW
通讯作者：
Dickson DW
影响因子：
11.2
作者：
Boeve, BF;Lang, AE;Litvan, I
通讯作者：
Litvan, I