Koga Shunsuke, Sanchez-Contreras Monica, Josephs Keith A, Uitti Ryan J, Graff-Radford Neill, van Gerpen Jay A, Cheshire William P, Wszolek Zbigniew K, Rademakers Rosa, Dickson Dennis W
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Department of Neurology (Behavioral Neurology & Movement Disorders), Mayo Clinic, Rochester, Minnesota, USA.
Mov Disord. 2017 Feb;32(2):246-255. doi: 10.1002/mds.26809. Epub 2016 Dec 23.
This study aimed to determine the frequency of transactive response DNA binding protein 43 kDa pathology in PSP, the clinical features of patients with this pathology, and genetic risk factors for it.
Hippocampal sections were screened with immunohistochemistry for transactive response DNA binding protein 43 kDa in 945 PSP cases. A subset of 261 cases that were negative in hippocampus was screened in the amygdala. The density and disruption of this pathology, as well as regional tau burden, and clinical and genetic characteristics were analyzed.
We observed transactive response DNA binding protein 43 kDa pathology in 47 cases in the hippocampus and an additional 9 cases that only affected the amygdala. Hippocampal sclerosis was the strongest risk factor, followed by Alzheimer's disease pathology, argyrophilic grain disease, and older age at death. Five stages of transactive response DNA binding protein 43 kDa pathology were identified in PSP: Stage A had pathology only in the amygdala (16%); stage I had pathology confined to the hippocampus and entorhinal cortex (9%); stage II included both regions of stage A and I (38%); stage III spread further to medial occipitotemporal gyrus (20%); and stage IV had pathology in the dorsolateral frontal lobe (18%). Anatomical areas vulnerable to PSP pathology had varying degrees of this pathology in stage II and later. PSP with transactive response DNA binding protein 43 kDa pathology were older at disease onset and had lower median MMSE scores; however, the latter was driven by concurrent pathologies.
Distribution and clinical characteristics of transactive response DNA binding protein 43 kDa pathology in PSP were influenced by concurrent pathologies. This is the first study to observe that PSP-vulnerable regions are also susceptible to this non-tau pathology. © 2016 International Parkinson and Movement Disorder Society.
本研究旨在确定进行性核上性麻痹（PSP）中反应性DNA结合蛋白43 kDa病理改变的频率、具有该病理改变患者的临床特征及其遗传风险因素。
对945例PSP病例的海马切片进行免疫组织化学检测，以筛查反应性DNA结合蛋白43 kDa。对海马检测为阴性的261例病例的杏仁核进行筛查。分析这种病理改变的密度和破坏情况，以及区域tau蛋白负荷、临床和遗传特征。
我们在47例海马病例中观察到反应性DNA结合蛋白43 kDa病理改变，另有9例仅累及杏仁核。海马硬化是最强的风险因素，其次是阿尔茨海默病病理改变、嗜银颗粒病和较高的死亡年龄。在PSP中确定了反应性DNA结合蛋白43 kDa病理改变的五个阶段：A期仅杏仁核有病理改变（16%）；I期病理改变局限于海马和内嗅皮质（9%）；II期包括A期和I期的两个区域（38%）；III期进一步扩散至枕颞内侧回（20%）；IV期背外侧额叶有病理改变（18%）。在II期及以后，易受PSP病理改变影响的解剖区域有不同程度的这种病理改变。有反应性DNA结合蛋白43 kDa病理改变的PSP患者发病年龄较大，简易精神状态检查表（MMSE）中位数得分较低；然而，后者是由并发病理改变所致。
PSP中反应性DNA结合蛋白43 kDa病理改变的分布和临床特征受并发病理改变影响。这是首次观察到PSP易损区域也易受这种非tau蛋白病理改变影响的研究。© 2016国际帕金森病和运动障碍协会
