TDP-43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer disease.
TDP-43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer disease.
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DOI：
10.1007/s00401-010-0681-2
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发表时间：
2010-07
影响因子：
12.7
通讯作者：
Mesulam M
中科院分区：
文献类型：
--
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
原发性进行性失语（PPA）的临床综合征可以在尸检中与多种神经病理学诊断相关联。30%的病例有阿尔茨海默病（AD）的病理表现，大多数情况下是在通常的分布中，这违背了大脑行为组织的原则，因为失语症不是边缘疾病的症状。本研究探讨是否伴随TDP-43病理可以解决缺乏临床解剖一致性。本文研究了16例临床PPA和10例主要为非失语额颞叶痴呆（FTD），均伴有AD病理，以确定他们的非典型临床表型是否反映了额外的TDP-43病理的存在。对照组为27例病理性AD，临床表现为典型的可能AD的健忘症。伴随的TDP-43病理仅在三种FTD和PPA中被发现，但在一半以上的典型遗忘临床表型中被发现。各组合并分析，海马硬化（HS）与TDP-43病理密切相关。因此，病理性AD患者PPA和FTD的临床表型很少与TDP-43蛋白病变相关。此外，内侧颞叶TDP-43病理与HS的联系比临床表型更紧密。这些发现挑战了目前关于临床病理相关性的概念，特别是关于多种病理的作用。
The clinical syndrome of primary progressive aphasia (PPA) can be associated with a variety of neuropathologic diagnoses at autopsy. Thirty percent of cases have Alzheimer disease (AD) pathology, most often in the usual distribution, which defies principles of brain–behavior organization, in that aphasia is not symptomatic of limbic disease. The present study investigated whether concomitant TDP-43 pathology could resolve the lack of clinicoanatomic concordance. In this paper, 16 cases of clinical PPA and 10 cases of primarily non-aphasic frontotemporal dementia (FTD), all with AD pathology, were investigated to determine whether their atypical clinical phenotypes reflected the presence of additional TDP-43 pathology. A comparison group consisted of 27 cases of pathologic AD with the typical amnestic clinical phenotype of probable AD. Concomitant TDP-43 pathology was discovered in only three of the FTD and PPA but in more than half of the typical amnestic clinical phenotypes. Hippocampal sclerosis (HS) was closely associated with TDP-43 pathology when all groups were combined for analysis. Therefore, the clinical phenotypes of PPA and FTD in cases with pathologic AD are only rarely associated with TDP-43 proteinopathy. Furthermore, medial temporal TDP-43 pathology is more tightly linked to HS than to clinical phenotype. These findings challenge the current notions about clinicopathologic correlation, especially about the role of multiple pathologies.
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影响因子：
64.8
作者：
Cruts, Marc;Gijselinck, Ilse;Van Broeckhoven, Christine
通讯作者：
Van Broeckhoven, Christine
影响因子：
30.8
作者：
Farrer MJ;Hulihan MM;Kachergus JM;Dächsel JC;Stoessl AJ;Grantier LL;Calne S;Calne DB;Lechevalier B;Chapon F;Tsuboi Y;Yamada T;Gutmann L;Elibol B;Bhatia KP;Wider C;Vilariño-Güell C;Ross OA;Brown LA;Castanedes-Casey M;Dickson DW;Wszolek ZK
通讯作者：
Wszolek ZK
DOI：
10.1097/nen.0b013e3181609361
发表时间：
2008-01-01
影响因子：
3.2
作者：
Freeman, Stefanie H.;Spires-Jones, Tara;Frosch, Matthew P.
通讯作者：
Frosch, Matthew P.
影响因子：
12.7
作者：
Miklossy, Judith;Steele, John C.;McGeer, Patrick L.
通讯作者：
McGeer, Patrick L.
影响因子：
6
作者：
Cairns, Nigel J.;Neumann, Manuela;Mackenzie, Ian R. A.
通讯作者：
Mackenzie, Ian R. A.