Signature tau neuropathology in gray and white matter of corticobasal degeneration
Signature tau neuropathology in gray and white matter of corticobasal degeneration
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DOI：
10.1016/s0002-9440(10)61154-6
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发表时间：
2002-06-01
影响因子：
6
通讯作者：
Trojanowski, JQ
中科院分区：
文献类型：
--
作者：
Forman, MS;Zhukareva, V;Trojanowski, JQ
皮质基底节变性 (CBD) 是一种成人发病的进行性神经退行性疾病，其特征为左旋多巴抵抗性强直、局灶性皮质缺损和可变性痴呆。 CBD 的神经病理学特征是神经元和神经胶质细胞中丝状包涵体的沉积，该丝状包涵体由高度磷酸化的 tau 蛋白组成，只有四个微管结合重复序列 (4R-tau)。为了表征 CBD 中 tau 病理学的区域负担，我们使用生化和组织化学技术研究了 12 个具有 CBD 神经病理学诊断的大脑。评估了 11 个大脑区域，包括额叶、顶叶、颞叶、枕叶、小脑以及基底神经节的灰质和白质。尽管 tau 病理学分布各不相同，但神经病理学和生化数据显示，两个半球的额叶、颞叶、顶叶和基底神经节的 tau 异常负担相似。这包括在两个或多个皮质区域和基底神经节的灰质和白质中以及较小程度上的小脑白质中存在丰富的、肌氨酰不溶性的4R-tau。灰质和白质中不溶性 tau 蛋白病理表现出重叠但不同的磷酸化表位；表明 tau 磷酸化存在细胞类型和亚细胞定位（即细胞体与细胞突起）特异性差异。相反，可溶性 tau 由正常的 4R/3R-tau 比例组成，表明 tau 剪接没有明显异常。因此，尽管临床上存在异质性，CBD 是一种独特的脑叶和基底神经节 tau 病，具有 4R-tau 选择性聚集。
Corticobasal degeneration (CBD) is an adult-onset progressive neurodegenerative disorder characterized by L-dopa-resistant rigidity, focal cortical deficits, and variable dementia. The neuropathological hallmark of CBD is the deposition of filamentous inclusions in neurons and glia composed of hyperphosphorylated tau with only four microtubule-binding repeats (4R-tau). To characterize the regional burden of tau pathology in CBD, we studied 12 brains with the neuropathological diagnosis of CBD using biochemical and histochemical techniques. Eleven brain regions were evaluated including gray and white matter from frontal, parietal, temporal, and occipital lobes and cerebellum as well as basal ganglia. Although the distribution of tau pathology was variable, neuropathological and biochemical data showed a similar burden of tau abnormalities in frontal, temporal, and parietal lobes and basal ganglia of both hemispheres. This included abundant, sarkosyl-insoluble 4R-tau in both gray and white matter of two or more of these cortical regions and basal ganglia, and to a lesser extent, cerebellar white matter. The insoluble tau pathology in gray and white matter showed overlapping but distinct phosphorylated epitopes; suggesting cell-type and subcellular localization (ie, cell bodies versus cell processes)-specific differences in tau phosphorylation. in contrast, soluble tau was composed of normal 4R/3R-tau ratios indicating no gross abnormality in tau splicing. Thus, although clinically heterogeneous, CBD is a distinct lobar and basal ganglionic tauopathy with selective aggregation of 4R-tau.