LEVELS OF NORMAL AND ABNORMALLY PHOSPHORYLATED-TAU IN DIFFERENT CELLULAR AND REGIONAL COMPARTMENTS OF ALZHEIMER-DISEASE AND CONTROL BRAINS
LEVELS OF NORMAL AND ABNORMALLY PHOSPHORYLATED-TAU IN DIFFERENT CELLULAR AND REGIONAL COMPARTMENTS OF ALZHEIMER-DISEASE AND CONTROL BRAINS
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DOI：
10.1016/0014-5793(94)00829-9
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发表时间：
1994-08-29
期刊：
影响因子：
3.5
通讯作者：
IQBAL, K
中科院分区：
文献类型：
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作者：
KHATOON, S;GRUNDKEIQBAL, I;IQBAL, K
微管相关蛋白tau在阿尔茨海默病（AD）脑中异常磷酸化。在本研究中，我们调查了（i）tau是否是轴突或轴突和体树突，（ii）tau是否是阿尔茨海默病神经病理学的标志物，以及（iii）AD脑细胞质（100，000 x g上清液）中tau的水平是否改变。本文分析了20例AD、17例正常老年人和15例神经系统正常者死后3- 8h的冰冻尸检组织。使用mAb Tau-1作为一抗，通过放射免疫印迹测定法测定正常、总和异常磷酸化tau的水平。来自正常脑的额叶灰质匀浆和胞质溶胶两者具有比来自白色物质的相应部分高30-45%的正常tau水平。AD患者额叶和颞叶皮质中tau蛋白的总含量是小脑皮质的6 ~ 7倍（P < 0.01和P < 0.02）。此外，小脑皮质的tau蛋白水平，一个不受阿尔茨海默氏症神经病理学变化影响的大脑区域，在AD和对照组之间是无法区分的。AD患者额叶灰质和白色区胞浆中正常tau蛋白水平均降低约40%（P < 0.05）。AD患者额叶和颞叶皮质中总tau蛋白水平比对照组相应组织中高4- 5倍（P < 0.01），这种增加是以异常磷酸化tau蛋白的形式出现的。这些研究表明：（i）体树突隔室中的tau可能至少与轴突隔室中的tau一样多，（ii）异常磷酸化的tau是AD中神经病理学的生化标志物，以及（iii）AD病例的100，000 x g脑上清液中正常tau的水平显著降低。
Microtubule associated protein tau is abnormally phosphorylated in Alzheimer disease (AD) brain. In the present study we investigated (i) whether tau is axonal or both axonal and somatodendritic, (ii) whether tau is a marker of Alzheimer neurofibrillary pathology, and (iii) whether the levels of tau in the cytosol (100,000 x g supernate) from AD brain are altered. Frozen autopsied tissue from 20 AD, 17 normal aged and 15 neurological control cases obtained 3-8 h postmortem were analyzed. Levels of normal, total, and abnormally phosphorylated tau were determined by a radioimmunoslot-blot assay using mAb Tau-1 as the primary antibody. Both frontal gray matter homogenate and cytosol from normal brains had 30-45% higher levels of normal tau than the corresponding fractions from the white matter. In AD frontal and temporal cortices, the total tau levels were 6- to 7-fold higher than in cerebellar cortex (P < 0.01 and P < 0.02). Furthermore, tau levels of cerebellar cortex, an area of the brain unaffected with Alzheimer neurofibrillary changes, were indistinguishable between AD and control groups. The levels of normal tau in cytosol from both frontal gray and white matters in AD were reduced by approximately 40% (P < 0.05). The levels of total tau in AD frontal and temporal cortex were 4- to 5-fold higher than in the corresponding tissue from control cases (P < 0.01) and this increase was in the form of abnormally phosphorylated tau. These studies suggest (i) that there is probably at least as much tau in the somatodendritic compartment as in the axonal compartment, (ii) that the abnormally phosphorylated tau is a biochemical marker of the neurofibrillary pathology in AD, and (iii) that the levels of normal tau are significantly reduced in the 100,000 x g brain supernate from AD cases.