Jung Youngsin, Dickson Dennis W, Murray Melissa E, Whitwell Jennifer L, Knopman David S, Boeve Bradley F, Jack Clifford R, Parisi Joseph E, Petersen Ronald C, Josephs Keith A
Department of Neurology (Behavioral Neurology), Mayo Clinic, Rochester, MN, USA.
J Neurol. 2014 Jul;261(7):1344-8. doi: 10.1007/s00415-014-7352-5. Epub 2014 Apr 24.
Widespread deposition of TAR DNA-binding protein of 43 kDa (TDP-43), a major protein inclusion commonly found in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) can also be seen in a subset of cases with Alzheimer's disease (AD). Some of these AD cases have TDP-43 immunoreactivity in basal ganglia (BG) and substantia nigra (SN), regions that when affected can be associated with parkinsonian signs or symptoms, or even features suggestive of frontotemporal dementia. Here, we examined the presence of clinical features of FTLD, parkinsonian signs and symptoms, and BG atrophy on MRI, in 51 pathologically confirmed AD cases (Braak neurofibrillary tangle stage IV-VI) with widespread TDP-43 deposition, with and without BG and SN involvement. All 51 cases had presented with progressive cognitive impairment with prominent memory deficits. None of the patients demonstrated early behavioral disinhibition, apathy, loss of empathy, stereotyped behavior, hyperorality, and/or executive deficits. Furthermore, TDP-43 deposition in BG or SN had no significant association with tremor (p = 0.80), rigidity (p = 0.19), bradykinesia (p = 0.19), and gait/postural instability (p = 0.39). Volumes of the BG structures were not associated with TDP-43 deposition in the BG. The present study demonstrates that TDP-43 deposition in pathologically confirmed AD cases is not associated with a clinical manifestation suggestive of FTLD, or parkinsonian features.
43 kDa的TAR DNA结合蛋白（TDP - 43）广泛沉积，这是一种常见于额颞叶变性（FTLD）和肌萎缩侧索硬化（ALS）的主要蛋白包涵体，在一部分阿尔茨海默病（AD）病例中也可见到。其中一些AD病例在基底神经节（BG）和黑质（SN）有TDP - 43免疫反应性，这些区域受影响时可能与帕金森氏体征或症状相关，甚至出现提示额颞叶痴呆的特征。在此，我们检查了51例经病理证实为AD（Braak神经原纤维缠结分期IV - VI）且有广泛TDP - 43沉积、伴有或不伴有BG和SN受累的病例，观察其FTLD的临床特征、帕金森氏体征和症状以及MRI上BG萎缩情况。所有51例均表现为进行性认知障碍且有明显记忆缺陷。没有患者表现出早期行为抑制、冷漠、共情缺失、刻板行为、口欲亢进和/或执行功能缺陷。此外，BG或SN中的TDP - 43沉积与震颤（p = 0.80）、强直（p = 0.19）、运动迟缓（p = 0.19）和步态/姿势不稳（p = 0.39）无显著相关性。BG结构的体积与BG中TDP - 43沉积无关。本研究表明，在经病理证实的AD病例中，TDP - 43沉积与提示FTLD的临床表现或帕金森氏特征无关。
