NEUROFILAMENT MONOCLONAL-ANTIBODIES RT97 AND 8D8 RECOGNIZE DIFFERENT MODIFIED EPITOPES IN PAIRED HELICAL FILAMENT-TAU IN ALZHEIMERS-DISEASE
NEUROFILAMENT MONOCLONAL-ANTIBODIES RT97 AND 8D8 RECOGNIZE DIFFERENT MODIFIED EPITOPES IN PAIRED HELICAL FILAMENT-TAU IN ALZHEIMERS-DISEASE
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DOI：
10.1111/j.1471-4159.1993.tb03298.x
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发表时间：
1993-04-01
影响因子：
4.7
通讯作者：
ANDERTON, BH
中科院分区：
文献类型：
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作者：
BRION, JP;COUCK, AM;ANDERTON, BH
先前已经发现阿尔茨海默病中的神经纤维缠结被一些也识别tau蛋白的神经丝抗体标记。我们已经研究了两个这样的单克隆抗体，RT 97和8D 8，和抗泛素血清与异常的成对螺旋丝（PHF）-tau（A68）多肽的反应性，已知是构成神经元缠结的PHF的主要成分。8D 8识别三种主要的PHF-tau多肽，但RT 97仅与两种较大的PHF-tau种类反应。PHF-tau多肽被8D 8和RT 97标记的强度比正常人tau强得多，并且这种标记在碱性磷酸酶处理后降低。抗泛素和抗磷酸酪氨酸抗体不标记PHF-tau多肽。用RT 97、8D 8和一组tau抗体研究PHF-tau多肽的蛋白水解片段的免疫反应性。PHF-tau上的8D 8的表位位于tau的羧基一半中的氨基酸222和427之间。PHF-tau上的RT 97表位定位于tau的氨基结构域中，可能在朝向一些tau同种型的氨基末端发现的29个氨基酸插入（插入1）中。这些结果表明，通过抗体8D 8和RT 97标记神经丝的神经纤维缠结的基础是它们通过识别PHF-tau上特异性修饰的位点（包括对某些T同种型特异性的位点）与PHF-tau多肽反应的能力。
Neurofibrillary tangles in Alzheimer's disease have been previously found to be labeled by some neurofilament antibodies that also recognize tau proteins. We have studied the reactivity of two such monoclonal antibodies, RT97 and 8D8, and of an anti-ubiquitin serum with the abnormal paired helical filaments (PHF)-tau (A68) polypeptides known to be the main component of the PHFs constituting the neurofibrillary tangles. 8D8 recognized the three major PHF-tau polypeptides, but RT97 reacted only with the two larger PHF-tau species. PHF-tau polypeptides were labeled by 8D8 and RT97 much more strongly than normal human tau and this labeling was decreased after alkaline phosphatase treatment. Anti-ubiquitin and anti-phosphotyrosine antibodies did not label PHF-tau polypeptides. The immunoreactivity of proteolytic fragments of PHF-tau polypeptides was studied with RT97, 8D8, and a panel of tau antibodies. The epitope for 8D8 on PHF-tau was localized between amino acids 222 and 427 in the carboxyl half of tau. The RT97 epitope on PHF-tau was localized in the amino domain of tau, probably in the 29-amino-acid insertion (insert 1) found towards the amino terminus of some tau isoforms. These results show that the basis for the labeling of neurofibrillary tangles by antibodies 8D8 and RT97 to neurofilament is their ability to react with PHF-tau polypeptides by recognizing sites specifically modified on PHF-tau, including a site specific to some T isoforms.