PATHOLOGICAL PROTEINS TAU-64 AND TAU-69 ARE SPECIFICALLY EXPRESSED IN THE SOMATODENDRITIC DOMAIN OF THE DEGENERATING CORTICAL-NEURONS DURING ALZHEIMERS-DISEASE - DEMONSTRATION WITH A PANEL OF ANTIBODIES AGAINST TAU-PROTEINS
PATHOLOGICAL PROTEINS TAU-64 AND TAU-69 ARE SPECIFICALLY EXPRESSED IN THE SOMATODENDRITIC DOMAIN OF THE DEGENERATING CORTICAL-NEURONS DURING ALZHEIMERS-DISEASE - DEMONSTRATION WITH A PANEL OF ANTIBODIES AGAINST TAU-PROTEINS
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DOI：
10.1007/bf00308912
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发表时间：
1990-01-01
影响因子：
12.7
通讯作者：
DEFOSSEZ, A
中科院分区：
文献类型：
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作者：
DELACOURTE, A;FLAMENT, S;DEFOSSEZ, A
成对螺旋丝束（PHF）聚集在阿尔茨海默病期间退化的锥体神经元中。这种神经退行性变与痴呆的临床体征高度相关。在此变性过程中，作为PHF主要抗原组分的Tau蛋白异常磷酸化，并表达两种名为Tau 64和69的病理同种型。我们研究了它们在正常和阿尔茨海默病大脑不同区域的皮质灰质和白色物质中的免疫印迹分布，以确定退化过程是否优先影响体树突或轴突域。使用两类抗体。第一类由抗人天然Tau、来自不同脊椎动物的抗Tau蛋白、抗PHF、单克隆抗体Alz-50和抗Tau的C末端重复区组成。在对照脑中，这些抗体强烈检测到灰质中的正常Tau蛋白，而Tau免疫检测在白色物质中较弱。在阿尔茨海默氏症脑皮质中，每种抗体在灰质提取物中检测到Tau 64和69，但在白色物质提取物中根本检测不到。第二类抗Tau由用正常脑蛋白提取物饱和的抗PHF组成。该抗血清仅探测异常磷酸化的Tau蛋白。它只在阿尔茨海默氏症大脑的皮质灰质中检测到Tau 64和69。此外，55-kDa的Tau蛋白也被免疫标记，这可能是正常Tau和Tau 64和69之间的中间形式。我们的研究结果表明，Tau蛋白是正常的，是体树突结构域的主要组成部分，Tau病理，反映了Tau 64和69的存在，在阿尔茨海默病期间优先影响该结构域。
Bundles of paired helical filaments (PHF) accumulate in the pyramidal neurons that degenerate during Alzheimer''s disease. This neurofibrillary degeneration is highly correlated with clinical signs of dementia. During this degeneration process, Tau proteins, which are the major antigenic components of PHF, are abnormally phosphorylated and two pathological isoforms named Tau 64 and 69 are expressed. We have studied their immunoblot distribution in the cortical gray and white matter from different reginons of normal and Alzheimer brains, to determine if the degenerating process preferentially affects the somatodendritic or the axonal domain. Two categories of antibodies were used. The first category consisted of anti-human native Tau, anti-Tau proteins from different vertebrates, anti-PHF, monoclonal antibody Alz-50 and an anti-C terminal repeated region of Tau. In control brains, these antibodies strongly detected normal Tau proteins in the gray matter while Tau immunodetection was weak in the white matter. In Alzheimer brain cortices, each antibody detected Tau 64 and 69 in gray matter extracts but not at all in white matter extracts. The second category of anti-Tau consisted of the anti-PHF saturated with normal brain protein extracts. This antiserum only probed the abnormally phosphorylated Tau proteins. It detected Tau 64 and 69 exclusively in the cortical gray matter of Alzheimer brains. Moreover, a 55-kDa Tau protein was also immunolabelled, which might be an intermediary form between normal Tau and Tau 64 and 69. Our results demonstrate that Tau proteins are normal and major components of the somatodendritic domain and that Tau pathology, reflected by the presence of Tau 64 and 69, affects preferentially this domain during Alzheimer''s disease.