Lauckner Jane, Frey Peter, Geula Changiz
Laboratory for Neurodegenerative and Aging Research, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Neurobiol Aging. 2003 Oct;24(6):767-76. doi: 10.1016/s0197-4580(02)00228-2.
The Phospho-Ser(262) epitope of phosphorylated tau, which accumulates in tangles in Alzheimer's disease (AD) brains, has been shown to have a strong disruptive effect on microtubules. Using antibodies which specifically recognize the Phospho-Ser(262) of tau, we compared the presence of this epitope in normal appearing neurons (pre-tangles) and tangles, with the presence of Phospho-Ser(199/202) (AT-8) and Phospho-Ser(396/404) (PHF-1) epitopes. All antibodies visualized lightly or darkly stained pre-tangles, neurons with immunoreactive clumps, intracellular and extracellular tangles. Pre-tangles were more abundant in control cases which showed some pathology, when compared with AD brains. Immunoreactivity for Phospho-Ser(262) was preferentially present in intracellular and extracellular tangles and was found in a significantly smaller number of pre-tangles when compared with the other epitopes. These results indicate the presence of various epitopes of Phospho-Tau in a substantial number of pre-tangles which may represent an early marker of tangle formation. The differential distribution of various epitopes suggests that the presence of the Phospho-Ser(262) epitope of tau either accelerates the transition form pre-tangle to tangle, or appears later than the other epitopes in the process of tangle formation.
在阿尔茨海默病（AD）大脑中缠结部位积累的磷酸化tau蛋白的磷酸化丝氨酸（262）表位，已被证明对微管具有强烈的破坏作用。我们使用特异性识别tau蛋白磷酸化丝氨酸（262）的抗体，将该表位在正常外观神经元（缠结前）和缠结中的存在情况，与磷酸化丝氨酸（199/202）（AT-8）和磷酸化丝氨酸（396/404）（PHF-1）表位的存在情况进行了比较。所有抗体都能使轻度或重度染色的缠结前神经元、具有免疫反应性团块的神经元、细胞内和细胞外缠结可视化。与AD大脑相比，在有一些病理表现的对照病例中，缠结前神经元更为丰富。与其他表位相比，磷酸化丝氨酸（262）的免疫反应性优先存在于细胞内和细胞外缠结中，且在数量明显较少的缠结前神经元中发现。这些结果表明，在大量缠结前神经元中存在磷酸化tau蛋白的各种表位，这可能代表缠结形成的早期标志物。各种表位的差异分布表明，tau蛋白磷酸化丝氨酸（262）表位的存在要么加速了从缠结前到缠结的转变，要么在缠结形成过程中比其他表位出现得更晚。
