Greater Manchester Neurosciences Centre, Hope Hospital, University of Manchester, Salford, UK.
Acta Neuropathol. 2010 Jul;120(1):55-66. doi: 10.1007/s00401-010-0702-1. Epub 2010 May 30.
TDP-43 is characteristically accumulated in TDP-43 proteinopathies such as frontotemporal lobar degeneration and motor neurone disease, but is also present in some tauopathies, including Alzheimer's disease, argyrophilic grain disease, and corticobasal degeneration (CBD). However, several studies have suggested that cases of progressive supranuclear palsy (PSP) lack TDP-43 pathology. We have therefore examined limbic regions of the brain in 19 PSP cases, as well as in 12 CBD cases, using phosphorylation-dependent anti-TDP-43 antibodies. We observed TDP-43-positive inclusions in five PSP cases (26%), as well as in two CBD cases (17%). The amygdala and hippocampal dentate gyrus were most frequently affected in PSP. Regional tau burden tended to be higher in TDP-43-positive PSP cases, and a significant correlation between tau and TDP-43 burden was noted in the occipitotemporal gyrus. Hippocampal sclerosis (HS) was found in 3/5 TDP-43-positive PSP cases, but HS was significantly more frequent in TDP-43-positive than TDP-43 negative PSP cases. Dementia was present in 13/19 (58%) of the PSP cases, in 4/5 TDP-43-positive cases, in all 3 TDP-43-positive cases with HS, in 1/2 TDP-43-positive cases without HS, and 7/14 cases lacking both. TDP-43 and tau were frequently colocalized in the amygdala, but not in the hippocampal dentate gyrus. Immunoblotting demonstrated the characteristic (for TDP-43 proteinopathies) 45 and 25 kDa bands and high molecular weight smear in the TDP-43-positive PSP case. These findings suggest that (1) although PSP is nominally a tauopathy, pathological TDP-43 can accumulate in the limbic system in some cases, and (2) TDP-43 pathology may be concurrent with HS.
TDP-43 通常在 TDP-43 蛋白病中积累，如额颞叶变性和运动神经元病，但也存在于一些 tau 病中，包括阿尔茨海默病、颗粒状嗜银病和皮质基底节变性（CBD）。然而，一些研究表明，进行性核上性麻痹（PSP）病例缺乏 TDP-43 病理学。因此，我们使用磷酸化依赖性抗 TDP-43 抗体检查了 19 例 PSP 病例和 12 例 CBD 病例的脑边缘区。我们在 5 例 PSP 病例（26%）和 2 例 CBD 病例（17%）中观察到 TDP-43 阳性包涵体。PSP 中最常受影响的区域是杏仁核和海马齿状回。TDP-43 阳性 PSP 病例的区域 tau 负担往往较高，在颞枕叶中观察到 tau 和 TDP-43 负担之间存在显著相关性。在 3/5 的 TDP-43 阳性 PSP 病例中发现了海马硬化（HS），但 TDP-43 阳性 PSP 病例的 HS 频率明显高于 TDP-43 阴性 PSP 病例。在 19 例 PSP 病例中有 13 例（58%）存在痴呆，在 5 例 TDP-43 阳性病例中有 4 例，在所有 3 例伴有 HS 的 TDP-43 阳性病例中有 3 例，在 2 例不伴有 HS 的 TDP-43 阳性病例中有 1 例，在不伴有 TDP-43 和 tau 的 14 例病例中有 7 例。TDP-43 和 tau 在杏仁核中经常共定位，但不在海马齿状回中。免疫印迹显示 TDP-43 阳性 PSP 病例中存在特征性（TDP-43 蛋白病）45 和 25 kDa 条带和高分子量弥散。这些发现表明：（1）尽管 PSP 是名义上的 tau 病，但在某些情况下，TDP-43 蛋白可以在边缘系统中积累，（2）TDP-43 病理学可能与 HS 并存。
