Kobayashi Katsuji, Nakano Hiroyuki, Hayashi Masahiro, Shimazaki Masao, Fukutani Yuken, Sasaki Kazuo, Sugimori Kaoru, Koshino Yoshifumi
Department of Psychiatry and Neurobiology, Graduate School of Medical Sciences, Kanazawa University, 13-1, Takara-machi, Ishikawa 920-8641, Japan.
J Neurol Sci. 2003 Apr 15;208(1-2):17-24. doi: 10.1016/s0022-510x(02)00410-0.
In addition to neuritic changes and amyloid deposits, neuronal and glial cell apoptosis is an important pathological feature of Alzheimer's disease (AD). Several factors have been postulated as causes or triggers of cellular apoptotic change. This study focused on a quantifiable relationship between phosphorylation sites of tau protein in the neurofibrillary tangles (NFT) and neuronal apoptosis. Five monoclonal anti-tau antibodies (AT180, AT8, HT7, Tau2 and Tau5) for NFT labeling and TdT-mediated UTP nick-end labeling (TUNEL) for localizing apoptotic change were employed. TUNEL-stained neuronal nuclei showed significantly high density in the entorhinal cortex, cornu ammonis (CA) and the parietal cortex. In all regions, density of TUNEL-stained neuronal nuclei showed significantly direct correlation with that of AT8-, AT180- and Tau2-positive neurons. Correlation of TUNEL-stained neuronal nuclei with tau-positive neurons differed depending on the cerebral regions. Density of TUNEL-stained neuronal nuclei showed inverse correlation with that of both AT8-positive and Gallyas-stained NFT in the CA and showed significantly direct correlation with AT8- and HT7-positive neurons in the frontal cortex. Density of tau-positive and Gallyas-stained NFT was higher than that of TUNEL-stained nuclei. We conclude that phosphorylation sites of tau, 159-163 and 202-205, are probably associated with neuronal apoptosis and apoptotic change follows abnormal phosphorylation of tau.
除了神经突变化和淀粉样蛋白沉积外，神经元和神经胶质细胞凋亡是阿尔茨海默病（AD）的一个重要病理特征。已经提出了几种因素作为细胞凋亡变化的原因或触发因素。本研究聚焦于神经原纤维缠结（NFT）中tau蛋白磷酸化位点与神经元凋亡之间的可量化关系。采用了五种用于NFT标记的单克隆抗tau抗体（AT180、AT8、HT7、Tau2和Tau5）以及用于定位凋亡变化的末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）。TUNEL染色的神经元细胞核在内嗅皮质、海马角（CA）和顶叶皮质中显示出显著的高密度。在所有区域，TUNEL染色的神经元细胞核密度与AT8、AT180和Tau2阳性神经元的密度呈显著正相关。TUNEL染色的神经元细胞核与tau阳性神经元的相关性因脑区而异。TUNEL染色的神经元细胞核密度在CA区与AT8阳性和加利亚斯染色的NFT密度呈负相关，而在额叶皮质与AT8和HT7阳性神经元密度呈显著正相关。tau阳性和加利亚斯染色的NFT密度高于TUNEL染色的细胞核密度。我们得出结论，tau蛋白的159 - 163和202 - 205磷酸化位点可能与神经元凋亡相关，并且凋亡变化继发于tau蛋白的异常磷酸化。
