Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Acta Neuropathol. 2011 Dec;122(6):727-36. doi: 10.1007/s00401-011-0888-x. Epub 2011 Oct 20.
Clinical and pathological evidence supports the notion that corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are distinct, but overlapping neurodegenerative tauopathies. Although both disorders are characterized by abnormal accumulation of 4-repeat tau, they display distinct proteolytic profiles of tau species and they have distinct astrocytic lesions, astrocytic plaques in CBD and tufted astrocytes in PSP. To investigate other differences between these two disorders at the molecular level, we compared the profiles of proteins from caudate nucleus of CBD and PSP by quantitative two-dimensional difference gel electrophoresis. Twenty-one protein spots differentially expressed in CBD and PSP were dissected for mass spectrometry (MS). One of the spots was identified by MS to contain light chain (LC) ferritin. Western blot analysis verified the presence of LC ferritin in this spot and showed that this protein was two-fold higher in caudate of CBD than that of PSP samples. These results were confirmed by LC ferritin immunohistochemistry. Co-labeling of caudate nucleus with tau and LC ferritin antibodies showed the presence of LC ferritin immunoreactivity in astrocytic plaques of CBD, but minimal labeling of tufted astrocytes in PSP. This difference did not reflect the extent of gliosis. Analysis of other brain regions in CBD and PSP showed no difference in LC ferritin levels. Together the data suggest that LC ferritin is a unique marker of astrocytic lesions in CBD, adding further support to the notion that CBD and PSP are distinct clinicopathologic entities.
临床和病理证据支持皮质基底节变性 (CBD) 和进行性核上性麻痹 (PSP) 是两种不同但重叠的神经退行性 tau 病的观点。虽然这两种疾病都以 4 重复 tau 的异常积累为特征，但它们显示出 tau 物种的不同蛋白水解谱，并且具有不同的星形胶质细胞病变，CBD 中的星形胶质细胞斑块和 PSP 中的丛状星形胶质细胞。为了在分子水平上研究这两种疾病之间的其他差异，我们通过定量二维差异凝胶电泳比较了 CBD 和 PSP 尾状核的蛋白质谱。从 CBD 和 PSP 中分离出 21 个差异表达的蛋白质斑点进行质谱 (MS) 分析。其中一个斑点被 MS 鉴定为包含轻链 (LC) 铁蛋白。Western blot 分析证实了该斑点中存在 LC 铁蛋白，并表明 CBD 尾状核中的 LC 铁蛋白含量是 PSP 样本的两倍。LC 铁蛋白免疫组织化学进一步证实了这一结果。尾状核与 tau 和 LC 铁蛋白抗体的共标记显示，LC 铁蛋白免疫反应性存在于 CBD 的星形胶质细胞斑块中，但 PSP 中的丛状星形胶质细胞标记很少。这种差异并不反映神经胶质增生的程度。对 CBD 和 PSP 中其他脑区的分析显示，LC 铁蛋白水平无差异。这些数据表明，LC 铁蛋白是 CBD 中星形胶质细胞病变的独特标志物，进一步支持 CBD 和 PSP 是两种不同的临床病理实体的观点。
