TDP-43 pathology, cognitive decline, and dementia in old age.
TDP-43 pathology, cognitive decline, and dementia in old age.
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DOI：
10.1001/jamaneurol.2013.3961
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发表时间：
2013-11
期刊：
影响因子：
29
通讯作者：
Schneider, Julie A.
中科院分区：
文献类型：
--
作者：
Wilson, Robert S.;Yu, Lei;Trojanowski, John Q.;Chen, Er-Yun;Boyle, Patricia A.;Bennett, David A.;Schneider, Julie A.
认知能力下降是老年残疾和死亡的主要原因，但其神经生物学基础尚不清楚。检验交互反应 DNA 结合蛋白 43 (TDP-43) 与晚年认知能力下降相关的假设。纵向临床病理队列研究。美国各地有 40 多个天主教团体。共有 130 名老年天主教修女、牧师和僧侣在死亡前平均 10.1 年接受年度临床评估，包括详细的认知测试。在神经病理学检查中，我们收集了来自多个大脑区域的 TDP-43 病理学、神经元神经原纤维缠结的密度、淀粉样蛋白斑块占据的面积以及 α-突触核蛋白路易体的存在的半定量测量结果。还发现了肉眼和显微镜下的脑梗塞和海马硬化。先前建立的全球认知综合测量在死亡前平均 10.1 年的年度观察期间的年变化率。 46% 的参与者发现 TDP-43 病理从稀疏到严重，与淀粉样蛋白斑、缠结和海马硬化有关，但与新皮质路易体或脑梗塞无关。在控制了淀粉样斑块、缠结和海马硬化后，TDP-43 病理学与更快速的认知能力下降相关，并且几乎与缠结一样解释了整体认知能力下降速率的变异性。 TDP-43 病理学具有与其他神经病理学过程不同的独特认知特征（与情景记忆和工作记忆下降有关，但与其他认知领域无关），并且在患有痴呆症的患者中升高，但在患有轻度认知障碍的患者中没有升高。结果表明，TDP-43 是导致老年认知衰退和痴呆的重要脑部病理学。
Cognitive decline is a leading cause of disability and death in old age but its neurobiological bases are not well understood. To test the hypothesis that transactive response DNA-binding protein 43 (TDP-43) is related to late life cognitive decline. Longitudinal clinical-pathologic cohort study. More than 40 Catholic groups across the United States. A total of 130 older Catholic nuns, priests, and monks underwent annual clinical evaluations, including detailed cognitive testing, for a mean of 10.1 years prior to death. On neuropathologic examination, we collected semiquantitative measures of TDP-43 pathology, density of neuronal neurofibrillary tangles, area occupied by amyloid-beta plaques, and the presence of alpha-synuclein Lewy bodies from multiple brain regions. Gross and microscopic cerebral infarcts and hippocampal sclerosis were also identified. Annual rate of change in a previously established composite measure of global cognition during a mean of 10.1 years of annual observation before death. TDP-43 pathology ranging from sparse to severe was identified in 46% of participants and was associated with amyloid plaques, tangles, and hippocampal sclerosis but not neocortical Lewy bodies or cerebral infarcts. After controlling for amyloid plaques, tangles, and hippocampal sclerosis, TDP-43 pathology was associated with more rapid cognitive decline and accounted for nearly as much of the variability in rates of global cognitive decline as did tangles. TDP-43 pathology had a distinct cognitive profile that differed from other neuropathologic processes (related to decline in episodic and working memory but not in other cognitive domains), and it was elevated in those who developed dementia but not in those with mild cognitive impairment. The results suggest that TDP-43 is an important brain pathology underlying cognitive decline and dementia in old age.
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影响因子：
12.7
作者：
Bigio EH;Mishra M;Hatanpaa KJ;White CL 3rd;Johnson N;Rademaker A;Weitner BB;Deng HX;Dubner SD;Weintraub S;Mesulam M
通讯作者：
Mesulam M
影响因子：
34.7
作者：
Lee, Edward B.;Lee, Virginia M-Y;Trojanowski, John Q.
通讯作者：
Trojanowski, John Q.
影响因子：
12.7
作者：
Neumann M;Kwong LK;Lee EB;Kremmer E;Flatley A;Xu Y;Forman MS;Troost D;Kretzschmar HA;Trojanowski JQ;Lee VM
通讯作者：
Lee VM
影响因子：
12.7
作者：
Arai, Tetsuaki;Mackenzie, Ian R. A.;Akiyama, Haruhiko
通讯作者：
Akiyama, Haruhiko
影响因子：
2.9
作者：
Higashi, Shinji;Iseki, Eizo;Arai, Heii
通讯作者：
Arai, Heii