Hu William T, Josephs Keith A, Knopman David S, Boeve Bradley F, Dickson Dennis W, Petersen Ronald C, Parisi Joseph E
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Acta Neuropathol. 2008 Aug;116(2):215-20. doi: 10.1007/s00401-008-0400-4. Epub 2008 Jul 1.
TAR DNA binding protein-43 (TDP-43) immunoreactive neuronal inclusions are detected in 20-30% of Alzheimer disease (AD) brains, but the distribution of this pathology has not been rigorously studied. In this report, we describe region-specific distribution and density of TDP-43 positive neuronal cytoplasmic inclusions (NCIs) in clinically demented individuals with high probability AD pathology, all with Braak neurofibrillary tangle stages of V or VI. Sections of hippocampus, amygdala, as well as temporal, frontal, and parietal neocortex, were analyzed with TDP-43 immunohistochemistry, and the density of NCIs was assessed using a semiquantitative scoring method. Of the 29 cases, six had TDP-43 positive NCIs in the amygdala only and seven had TDP-43 inclusions restricted to amygdala and hippocampus. In 16 cases, TDP-43 immunoreactivity was more widespread, affecting temporal, frontal or parietal neocortex. These findings indicate that medial temporal lobe limbic structures are vulnerable to TDP-43 pathology in advanced AD, and that the amygdala appears to be the most susceptible region. The distribution of the lesions in this cross-sectional analysis may suggest a progression of TDP-43 pathology in AD, with limbic structures in the medial temporal lobe affected first, followed by higher order association cortices.
在20%-30%的阿尔茨海默病（AD）患者大脑中可检测到TAR DNA结合蛋白43（TDP-43）免疫反应性神经元包涵体，但这种病理改变的分布尚未得到严格研究。在本报告中，我们描述了临床诊断为痴呆且极有可能患有AD病理改变（均处于Braak神经纤维缠结V期或VI期）的个体中，TDP-43阳性神经元胞质包涵体（NCI）的区域特异性分布及密度。采用TDP-43免疫组化方法分析海马、杏仁核以及颞叶、额叶和顶叶新皮质的切片，并使用半定量评分方法评估NCI的密度。在这29例病例中，6例仅在杏仁核中有TDP-43阳性NCI，7例的TDP-43包涵体局限于杏仁核和海马。在16例病例中，TDP-43免疫反应性分布更广泛，累及颞叶、额叶或顶叶新皮质。这些发现表明，在晚期AD中，内侧颞叶边缘结构易受TDP-43病理改变影响，且杏仁核似乎是最易受累的区域。在该横断面分析中病变的分布可能提示AD中TDP-43病理改变的进展过程，即内侧颞叶的边缘结构首先受累，随后是高级联合皮质。
