Phosphorylated TDP-43 pathology and hippocampal sclerosis in progressive supranuclear palsy.
Phosphorylated TDP-43 pathology and hippocampal sclerosis in progressive supranuclear palsy.
复制标题
DOI：
10.1007/s00401-010-0702-1
复制
发表时间：
2010-07
影响因子：
12.7
通讯作者：
Mann DM
中科院分区：
文献类型：
--
作者：
Yokota O;Davidson Y;Bigio EH;Ishizu H;Terada S;Arai T;Hasegawa M;Akiyama H;Sikkink S;Pickering-Brown S;Mann DM
TDP-43在TDP-43蛋白病如额颞叶变性和运动神经元病中典型地积累，但也存在于一些tau蛋白病，包括阿尔茨海默病、嗜银颗粒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）的病例缺乏TDP-43病理学。因此，我们研究了19例PSP病例和12例CBD病例的大脑边缘区，使用磷酸化依赖性抗TDP-43抗体。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。在PSP中，杏仁核和海马齿状回最常受到影响。TDP-43阳性PSP病例的区域tau负荷往往较高，并且在枕颞回中注意到tau和TDP-43负荷之间的显著相关性。5例TDP-43阳性PSP患者中3例出现海马硬化（HS），但TDP-43阳性PSP患者HS发生率明显高于TDP-43阴性PSP患者。13/19例PSP病例（58%）、4/5例TDP-43阳性病例、所有3例TDP-43阳性伴HS病例、1/2例TDP-43阳性不伴HS病例和7/14例两者均缺乏病例中存在痴呆。TDP-43和tau蛋白经常共定位于杏仁核，但不在海马齿状回。免疫印迹显示TDP-43阳性PSP病例中的特征性（TDP-43蛋白病）45和25 kDa条带和高分子量涂片。这些发现表明：（1）虽然PSP名义上是一种tau蛋白病，但在某些情况下，病理性TDP-43可在边缘系统中积累，以及（2）TDP-43病理可能与HS同时发生。
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.
登录
查看更多内容
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：
12.7
作者：
BRAAK, H;BRAAK, E
通讯作者：
BRAAK, E
影响因子：
12.7
作者：
Miklossy, Judith;Steele, John C.;McGeer, Patrick L.
通讯作者：
McGeer, Patrick L.
DOI：
10.1097/00005072-199904000-00006
发表时间：
1999-04-01
影响因子：
3.2
作者：
Bigio, EH;Brown, DF;White, CL
通讯作者：
White, CL
影响因子：
4.2
作者：
Ball, M;Braak, H;Khachaturian, Z
通讯作者：
Khachaturian, Z