Gómez-Ramos P, Morán M A
Department of Morphology, School of Medicine, Autónoma University of Madrid, Spain.
Microsc Res Tech. 1998 Oct 1;43(1):49-58. doi: 10.1002/(SICI)1097-0029(19981001)43:1<49::AID-JEMT8>3.0.CO;2-2.
Neurofibrillary tangles, one of the neuropathological signs of Alzheimer's disease, are frequently present in brains of aged nondemented people. Ultrastructurally, neurofibrillary tangles appear as paired helical and straight filaments. Both types of filaments, made of hyperphosphorylated tau protein, are present in neurons with neurofibrillary tangles. Neurons with neurofibrillary tangles have been described to undergo an evolution, starting with the accumulation of hyperphosphorylated tau, followed by the progressive appearance of both types of filaments, and ending in the death of the neuron. We ultrastructurally studied this evolution, using immunocytochemistry with an antibody against phosphorylated tau protein, in both nondemented aged and Alzheimer's disease brains. No differences were found between nondemented and demented brains, thus indicating the occurrence of the same process in both cases. Our results also suggest that hyperphosphorylated tau protein first appears as granular material, which becomes organized into short and disordered paired helical filaments. These filaments elongate and gradually become arranged into bundles whose core regions are occupied by straight filaments.
神经原纤维缠结是阿尔茨海默病的神经病理学标志之一，在老年非痴呆人群的大脑中也经常出现。在超微结构上，神经原纤维缠结表现为双螺旋丝和直丝。这两种类型的丝均由高度磷酸化的tau蛋白构成，存在于有神经原纤维缠结的神经元中。有神经原纤维缠结的神经元经历了一个演变过程，始于高度磷酸化tau的积累，接着是两种类型丝的逐渐出现，最终以神经元死亡告终。我们利用针对磷酸化tau蛋白的抗体进行免疫细胞化学，在非痴呆老年人和阿尔茨海默病患者的大脑中对这一演变过程进行了超微结构研究。未在非痴呆和痴呆大脑之间发现差异，因此表明在这两种情况下都发生了相同的过程。我们的结果还表明，高度磷酸化的tau蛋白最初表现为颗粒状物质，随后组织成短而无序的双螺旋丝。这些丝伸长并逐渐排列成束，其核心区域被直丝占据。
