Evaluation of subcortical pathology and clinical correlations in FTLD-U subtypes
Evaluation of subcortical pathology and clinical correlations in FTLD-U subtypes
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DOI：
10.1007/s00401-009-0547-7
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发表时间：
2009-09-01
影响因子：
12.7
通讯作者：
Dickson, Dennis W.
中科院分区：
文献类型：
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作者：
Josephs, Keith A.;Stroh, Alex;Dickson, Dennis W.
额颞叶变性可分为tau阳性(FTLD-tau)和tau阴性。最常见的tau阴性FTLD与由TAR DNA结合蛋白43(TDP-43)(FTLD-TDP)组成的神经元包涵体有关。最近的证据表明，FTLD-TDP至少可以根据TDP-43免疫反应阳性的神经元胞质包涵体(NCI)和营养不良神经元(DN)在大脑皮层和海马区的模式进一步细分为三种主要的组织学变体。本研究的目的是将组织学分析扩展到其他脑区，并确定FTLD-TDP亚型是否有明显的临床和病理特征。对39例FTLD-TDP患者进行分析，其中Mackenzie 1型24例，Mackenzie 2型9例，Mackenzie 3型6例。临床症状与FTLD-TDP亚型有高度相关性，进行性非流利性失语与1型相关，语义性痴呆与2型相关，行为变异型额颞部痴呆与1型、2型和3型相关。NCI和DN的半定量分析显示，皮质、皮质下和脑干区的受累模式不同，这三种类型的FTLD-TDP具有不同的特点。类型1表现为NCI和DN的混合体，多数病例核内包涵体和TDP-43病理见于神经轴的各个层面，但脑干少于幕上结构。2型以皮质长而粗的神经节为主，海马区、杏仁核和基底节可见大量NCI，间脑和脑干无NCI，仅有稀疏神经节。3型神经轴各节段的神经节细胞数均较少，舌下核神经节细胞数明显多于其他各型。这些发现扩展了先前描述的FTLD-TDP亚型的临床病理联系，并支持FTLD-TDP亚型可能是不同的临床病理疾病的观点。
Frontotemporal lobar degeneration (FTLD) can be classified as tau-positive (FTLD-tau) and tau-negative FTLD. The most common form of tau-negative FTLD is associated with neuronal inclusions that are composed of TAR DNA-binding protein 43 (TDP-43) (FTLD-TDP). Recent evidence suggests that FTLD-TDP can be further subdivided into at least three major histologic variants based on patterns of TDP-43 immunoreactive neuronal cytoplasmic inclusions (NCI) and dystrophic neurites (DN) in neocortex and hippocampus. The aim of this study was to extend the histologic analysis to other brain regions and to determine if there were distinct clinical and pathologic characteristics of the FTLD-TDP subtypes. Thirty-nine FTLD-TDP cases were analyzed (Mackenzie type 1 n = 24, Mackenzie type 2 n = 9, Mackenzie type 3 n = 6). There was a highly significant association between clinical syndrome and FTLD-TDP subtype, with progressive non-fluent aphasia associated with type 1, semantic dementia with type 2, and behavioral variant frontotemporal dementia with types 1, 2 and 3. Semi-quantitative analysis of NCI and DN demonstrated different patterns of involvement in cortical, subcortical and brainstem areas that were characteristic for each of the three types of FTLD-TDP. Type 1 had a mixture of NCI and DN, as well as intranuclear inclusions in most cases and TDP-43 pathology at all levels of the neuraxis, but less in brainstem than supratentorial structures. Type 2 cases were characterized by predominance of long, thick DN in the cortex, as well as numerous NCI in hippocampus, amygdala and basal ganglia, but virtually no NCI and only sparse DN in diencephalon and brainstem. Type 3 had a paucity of DN at all levels of the neuraxis and significantly more NCI in the hypoglossal nucleus than the other types. These findings extend previously described clinicopathological associations of FTLD-TDP subtypes and support the notion that FTLD-TDP subtypes may be distinct clinicopathologic disorders.