TDP-43 病理学与 ALS 认知：一项前瞻性临床病理关联研究。
TDP-43 pathology and cognition in ALS: A prospective clinicopathologic correlation study.
机构信息
From the Departments of Neurology (J.P.) and Psychosomatic Medicine (E.K., S.T.) and Institute of Forensic Medicine (A.B.), Rostock University Medical Center; German Center for Neurodegenerative Diseases (DZNE) (J.P., S.T.), Rostock; Institute of Medical Biostatistics, Epidemiology and Informatics (J.K.), University Medical Center, Johannes Gutenberg University Mainz, Germany; Quantitative Neuroimaging Group (C.S.), Academic Unit of Neurology, Biomedical Sciences Institute, Trinity College Dublin, Ireland; Department of Neuropathology (M.N.), University Hospital of Tübingen; and German Center for Neurodegenerative Diseases (DZNE) (M.N.), Tübingen, Germany.
出版信息
Neurology. 2016 Sep 6;87(10):1019-23. doi: 10.1212/WNL.0000000000003062. Epub 2016 Aug 3.
OBJECTIVE
Although a systematic spread of pathologic TDP-43 expression throughout the CNS in amyotrophic lateral sclerosis (ALS) has been proposed, the relationship between cognition and the extent and neuroanatomic distribution of TDP-43 pathology has not received considerable attention.
METHODS
We investigated the association between cognitive functioning and the extent of TDP-43 pathology in postmortem CNS tissue from 18 patients with ALS stratified into 3 groups based on detailed prospective neuropsychological testing (cognitively not impaired, n = 6; cognitively impaired, n = 6; ALS- frontotemporal dementia [FTD], n = 6) and analyzed these cases for clinicopathologic correlations.
RESULTS
Our findings demonstrate a close relationship between cognition and the extent of TDP-43 pathology in non-primary motor areas with a striking difference between ALS-FTD and the 2 other cognitive groups. The specificity of our results was underscored by 2 key findings: first, the absence of an Alzheimer pathology effect, a common confounder in older patients; second, the lack of correlations between the primary motor regions with the highest TDP-43 intensity and cognitive status.
CONCLUSIONS
Our data suggest a distinct dynamic of TDP-43 progression and distribution in ALS-FTD in contrast to ALS without FTD.
目的
虽然尸检研究已经提出，在肌萎缩侧索硬化症（ALS）患者的中枢神经系统（CNS）中，TDP-43 表达呈系统性扩散，但认知功能与 TDP-43 病理学的程度和神经解剖分布之间的关系尚未引起广泛关注。
方法
我们研究了 18 例 ALS 患者的认知功能与 TDP-43 病理学程度之间的关系，这些患者根据详细的前瞻性神经心理学测试分为 3 组（认知功能未受损组，n = 6；认知功能受损组，n = 6；ALS-额颞叶痴呆组，n = 6），并对这些病例进行了临床病理相关性分析。
结果
我们的发现表明，TDP-43 病理学程度与非主要运动区域的认知功能密切相关，ALS-FTD 与其他 2 个认知组之间存在显著差异。我们的研究结果有 2 个关键发现，强调了结果的特异性：首先，不存在阿尔茨海默病病理的影响，这是老年患者的常见混杂因素；其次，主要运动区域与 TDP-43 强度和认知状态之间没有相关性。
结论
我们的数据表明，与无额颞叶痴呆的 ALS 相比，ALS-FTD 中 TDP-43 的进展和分布具有明显不同的动态。
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