Pathological 43-kDa transactivation response DNA-binding protein in older adults with and without severe mental illness.
Pathological 43-kDa transactivation response DNA-binding protein in older adults with and without severe mental illness.
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DOI：
10.1001/archneurol.2010.254
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发表时间：
2010-10
影响因子：
--
通讯作者：
Trojanowski, John Q.
中科院分区：
文献类型：
--
作者：
Geser, Felix;Robinson, John L.;Malunda, Joseph A.;Xie, Sharon X.;Clark, Chris M.;Kwong, Linda K.;Moberg, Paul J.;Moore, Erika M.;Van Deerlin, Vivianna M.;Lee, Virginia M-Y;Arnold, Steven E.;Trojanowski, John Q.
精神分裂症和情绪障碍等主要精神疾病与特定的病理学无关，但其临床特征与额颞叶变性的行为变异的某些方面重叠。尽管病理性43 kDa（反式激活反应）DNA结合蛋白（TDP-43）对额颞叶变性的重要性最近才被认识到，但TDP-43病理在严重精神疾病患者与对照组中的患病率尚未得到系统的解决。检查慢性精神疾病患者，主要是精神分裂症，与对照组相比，神经退行性TDP-43病理学的证据。前瞻性纵向临床评价和回顾性病历审查，中枢神经系统病理性TDP-43的免疫组织化学鉴定，以及已知引起TDP-43蛋白病的基因改变（包括TDP-43（TARDBP）和颗粒蛋白前体（GRN）基因）的基因分型。大学卫生系统。151名受试者，包括91名严重精神疾病（主要是精神分裂症）患者和60名对照者。临床病历审查、神经元和神经胶质TDP-43病理学以及TARDP和GRN基因分型状态。在两组中，年龄小于65岁的受试者的杏仁核/杏仁核周围区或海马/经内嗅皮质中均不存在显著的TDP-43病理学，但在老年受试者中存在（29% [86例中的25例]精神病患者和29% [34例中的10例]对照受试者）。23%（35例中的8例）的阳性病例在扩展脑扫描中显示出显著的TDP-43病理学。在TDP-43病理学的频率、程度或形态学模式方面，两组之间没有明显差异。后者包括（1）软膜下和室管膜下，（2）局灶性或（3）脑深部实质弥漫性病变和（4）血管周围病变。在1例TDP-43病理性精神分裂症患者中发现一种意义不明的新GRN变异（c.620T>C，p.Met207Thr）。在本文研究的任何受试者中均未发现已知的TARDBP突变或其他变体。TDP-43病理学在患有严重精神疾病的老年患者和对照组中的类似发现表明边缘脑区域中常见的年龄依赖性TDP-43变化，这可能意味着这些区域在脑TDP-43多系统蛋白质病的早期过程中受到影响。最后，我们的数据提供了一个与年龄相关的基线发展全脑病理TDP-43的演变图式。
Major psychiatric diseases such as schizophrenia and mood disorders have not been linked to a specific pathology, but their clinical features overlap with some aspects of the behavioral variant of frontotemporal lobar degeneration. Although the significance of pathological 43-kDa (transactivation response) DNA-binding protein (TDP-43) for frontotemporal lobar degeneration was appreciated only recently, the prevalence of TDP-43 pathology in patients with severe mental illness vs controls has not been systematically addressed. To examine patients with chronic psychiatric diseases, mainlyschizophrenia, for evidence of neurodegenerative TDP-43 pathology in comparison with controls. Prospective longitudinal clinical evaluation and retrospective medical record review, immunohistochemical identification of pathological TDP-43 in the central nervous system, and genotyping for gene alterations known to cause TDP-43 proteinopathies including the TDP-43 (TARDBP) and progranulin (GRN) genes. University health system. One hundred fifty-one subjects including 91 patients with severe mental illness (mainly schizophrenia) and 60 controls. Clinical medical record review, neuronal and glial TDP-43 pathology, and TARDP and GRN genotyping status. Significant TDP-43 pathology in the amygdala/periamygdaloid region or the hippocampus/transentorhinal cortex was absent in both groups in subjects younger than 65 years but present in elderly subjects (29% [25 of 86] of the psychiatric patients and 29% [10 of 34] of control subjects). Twenty-three percent (8 of 35) of the positive cases showed significant TDP-43 pathology in extended brain scans. There were no evident differences between the 2 groups in the frequency, degree, or morphological pattern of TDP-43 pathology. The latter included (1) subpial and subependymal, (2) focal, or (3) diffuse lesions in deep brain parenchyma and (4) perivascular pathology. A new GRN variant of unknown significance (c.620T>C, p.Met207Thr) was found in 1 patient with schizophrenia with TDP-43 pathology. No known TARDBP mutations or other variants were found in any of the subjects studied herein. The similar findings of TDP-43 pathology in elderly patients with severe mental illness and controls suggest common age-dependent TDP-43 changes in limbic brain areas that may signify that these regions are affected early in the course of a cerebral TDP-43 multisystem proteinopathy. Finally, our data provide an age-related baseline for the development of whole-brain pathological TDP-43 evolution schemata.
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影响因子：
12.7
作者：
Foulds P;McAuley E;Gibbons L;Davidson Y;Pickering-Brown SM;Neary D;Snowden JS;Allsop D;Mann DM
通讯作者：
Mann DM
影响因子：
12.7
作者：
Kasai, Takashi;Tokuda, Takahiko;Nakagawa, Masanori
通讯作者：
Nakagawa, Masanori
影响因子：
12.7
作者：
Davidson, Yvonne;Amin, Hanan;Mann, David M. A.
通讯作者：
Mann, David M. A.
DOI：
10.1093/jnen/61.5.413
发表时间：
2002-05-01
影响因子：
3.2
作者：
Del Tredici, K;Rüb, U;Braak, H
通讯作者：
Braak, H
影响因子：
12.7
作者：
Brandmeir, Nicholas J.;Geser, Felix;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.