Flament S, Delacourte A, Verny M, Hauw J J, Javoy-Agid F
Unité INSERM 156, Lille, France.
Acta Neuropathol. 1991;81(6):591-6. doi: 10.1007/BF00296367.
We have previously shown that abnormal Tau species are produced during the neurofibrillary degeneration of the Alzheimer type. These abnormal Tau proteins consist of a characteristic triplet named Tau 55, Tau 64 and Tau 69 which are constantly found in Alzheimer's disease (AD) and Downs syndrome brain regions with tangles. To determine if abnormal Tau species are also produced in other neurodegenerative conditions where intraneuronal filamentous Tau aggregates are observed, we have undertaken an immuno-blot study of brain homogenates from patients with progressive supranuclear palsy (PSP), a neurological disorder characterized by the presence of tangles in subcortical and cortical brain areas. We show here that abnormal Tau species are produced in PSP but that they are different from those in AD. Indeed, although Tau 64 and 69 were present in PSP brain homogenates, possibly as the result of an abnormal phosphorylation as in AD, they were detected in smaller amounts (three times lower) than in AD. In addition Tau 55 was undetected by the immunological tools, such as the absorbed anti-PHF antisera, which specifically label the abnormal Tau proteins. Also the two-dimensional analysis revealed different isoelectric properties. Our results suggest that the production of abnormal Tau species is a very important event during all types of neurofibrillary degeneration. The differences in the pathological Tau-variant profile that were observed between PSP and AD possibly reflect different etiopathogenetic pathways and might explain the formation of different types of filamentous Tau aggregates.
我们之前已经表明，异常的 Tau 蛋白是在阿尔茨海默病类型的神经原纤维变性过程中产生的。这些异常的 Tau 蛋白由一个名为 Tau 55、Tau 64 和 Tau 69 的特征性三联体组成，它们在患有缠结的阿尔茨海默病（AD）和唐氏综合征脑区中经常被发现。为了确定在其他观察到神经元内丝状 Tau 聚集物的神经退行性疾病中是否也会产生异常的 Tau 蛋白，我们对进行性核上性麻痹（PSP）患者的脑匀浆进行了免疫印迹研究，PSP 是一种以皮质下和皮质脑区存在缠结为特征的神经系统疾病。我们在此表明，PSP 中会产生异常的 Tau 蛋白，但它们与 AD 中的不同。实际上，尽管 Tau 64 和 Tau 69 存在于 PSP 脑匀浆中，可能如同在 AD 中一样是异常磷酸化的结果，但它们的检测量比 AD 中的少（低三倍）。此外，通过诸如吸附的抗 PHF 抗血清等免疫工具未检测到 Tau 55，这些工具可特异性标记异常的 Tau 蛋白。而且二维分析揭示了不同的等电特性。我们的结果表明，异常 Tau 蛋白的产生是所有类型神经原纤维变性过程中的一个非常重要的事件。在 PSP 和 AD 之间观察到的病理性 Tau 变体谱的差异可能反映了不同的病因发病途径，并可能解释了不同类型丝状 Tau 聚集物的形成。
