以右半球语言优势为主的原发性进行性失语症中的非对称 TDP 病理学。
Asymmetric TDP pathology in primary progressive aphasia with right hemisphere language dominance.
机构信息
From the Cognitive Neurology and Alzheimer's Disease Center, Feinberg School of Medicine, Northwestern University, Chicago, IL.
出版信息
Neurology. 2018 Jan 30;90(5):e396-e403. doi: 10.1212/WNL.0000000000004891. Epub 2018 Jan 5.
OBJECTIVE
To quantitatively examine the regional densities and hemispheric distribution of the 43-kDa transactive response DNA-binding protein (TDP-43) inclusions, neurons, and activated microglia in a left-handed patient with right hemisphere language dominance and logopenic-variant primary progressive aphasia (PPA).
METHODS
Phosphorylated TDP-43 inclusions, neurons, and activated microglia were visualized with immunohistochemical and histologic methods. Markers were quantified bilaterally with unbiased stereology in language- and memory-related cortical regions.
RESULTS
Clinical MRI indicated cortical atrophy in the right hemisphere, mostly in the temporal lobe. Significantly higher densities of TDP-43 inclusions were present in right language-related temporal regions compared to the left or to other right hemisphere regions. The memory-related entorhinal cortex (ERC) and language regions without significant atrophy showed no asymmetry. Activated microglia displayed extensive asymmetry (R > L). A substantial density of neurons remained in all areas and showed no hemispheric asymmetry. However, perikaryal size was significantly smaller in the right hemisphere across all regions except the ERC. To demonstrate the specificity of this finding, sizes of residual neurons were measured in a right-handed case with PPA and were found to be smaller in the language-dominant left hemisphere.
CONCLUSIONS
The distribution of TDP-43 inclusions and microglial activation in right temporal language regions showed concordance with anatomic distribution of cortical atrophy and clinical presentation. The results revealed no direct relationship between density of TDP-43 inclusions and activated microglia. Reduced size of the remaining neurons is likely to contribute to cortical atrophy detected by MRI. These findings support the conclusion that there is no obligatory relationship between logopenic PPA and Alzheimer pathology.
目的
定量研究左利手、右侧大脑半球语言优势伴语义性痴呆型进行性失语症（PPA）患者大脑中 43kDa 转激活反应 DNA 结合蛋白（TDP-43）包涵体、神经元和激活小胶质细胞的区域性密度和半球分布。
方法
采用免疫组织化学和组织学方法显示磷酸化 TDP-43 包涵体、神经元和激活小胶质细胞。采用无偏立体学方法对与语言和记忆相关的皮质区域进行双侧标记定量。
结果
临床 MRI 显示右侧大脑半球皮质萎缩，主要在颞叶。与左侧或其他右侧大脑半球区域相比，右侧语言相关的颞叶区域 TDP-43 包涵体的密度明显更高。与记忆相关的内嗅皮质（ERC）和无明显萎缩的语言区域无不对称性。激活的小胶质细胞显示广泛的不对称性（右侧>左侧）。所有区域的神经元密度仍然很高，没有半球不对称性。然而，除了 ERC 之外，右侧大脑半球所有区域的神经元的胞体大小明显较小。为了证明这一发现的特异性，在右侧大脑半球优势伴 PPA 的右利手病例中测量了残留神经元的大小，发现它们在语言优势的左侧半球较小。
结论
TDP-43 包涵体和小胶质细胞激活在右侧颞叶语言区域的分布与皮质萎缩的解剖分布和临床表现一致。结果表明，TDP-43 包涵体的密度与激活的小胶质细胞之间没有直接关系。残留神经元的大小减小可能导致 MRI 检测到的皮质萎缩。这些发现支持这样的结论，即失语法性 PPA 与阿尔茨海默病病理学之间没有必然的关系。
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