Sasaki N, Fukatsu R, Tsuzuki K, Hayashi Y, Yoshida T, Fujii N, Koike T, Wakayama I, Yanagihara R, Garruto R, Amano N, Makita Z
Department of Neuropsychiatry, Sapporo Medical University, Japan.
Am J Pathol. 1998 Oct;153(4):1149-55. doi: 10.1016/S0002-9440(10)65659-3.
Advanced glycation end products (AGEs) have been implicated in the chronic complications of diabetes mellitus and have been reported to play an important role in the pathogenesis of Alzheimer's disease. In this study, we examined the immunohistochemical localization of AGEs, amyloid beta protein (A beta), apolipoprotein E (ApoE), and tau protein in senile plaques, neurofibrillary tangles (NFTs), and cerebral amyloid angiopathy (CAA) in Alzheimer's disease and other neurodegenerative diseases (progressive supranuclear palsy, Pick's disease, and Guamanian amyotrophic lateral sclerosis/Parkinsonism-dementia complex). In most senile plaques (including diffuse plaques) and CAA from Alzheimer's brains, AGE and ApoE were observed together. However, approximately 5% of plaques were AGE positive but A beta negative, and the vessels without CAA often showed AGE immunoreactivity. In Alzheimer's disease, AGEs were mainly present in intracellular NFTs, whereas ApoE was mainly present in extracellular NFTs. Pick's bodies in Pick's disease and granulovacuolar degeneration in various neurodegenerative diseases were also AGE positive. In non-Alzheimer neurodegenerative diseases, senile plaques and NFTs showed similar findings to those in Alzheimer's disease. These results suggest that AGE may contribute to eventual neuronal dysfunction and death as an important factor in the progression of various neurodegenerative diseases, including Alzheimer's disease.
晚期糖基化终末产物（AGEs）与糖尿病的慢性并发症有关，并且据报道在阿尔茨海默病的发病机制中起重要作用。在本研究中，我们检测了AGEs、β淀粉样蛋白（Aβ）、载脂蛋白E（ApoE）和tau蛋白在阿尔茨海默病及其他神经退行性疾病（进行性核上性麻痹、匹克病和关岛肌萎缩侧索硬化/帕金森病-痴呆综合征）的老年斑、神经原纤维缠结（NFTs）和脑淀粉样血管病（CAA）中的免疫组化定位。在大多数来自阿尔茨海默病大脑的老年斑（包括弥漫性斑块）和CAA中，AGE和ApoE同时被观察到。然而，约5%的斑块AGE阳性但Aβ阴性，且无CAA的血管常显示AGE免疫反应性。在阿尔茨海默病中，AGEs主要存在于细胞内NFTs中，而ApoE主要存在于细胞外NFTs中。匹克病中的匹克小体和各种神经退行性疾病中的颗粒空泡变性也为AGE阳性。在非阿尔茨海默神经退行性疾病中，老年斑和NFTs显示出与阿尔茨海默病相似的结果。这些结果表明，AGE可能作为包括阿尔茨海默病在内的各种神经退行性疾病进展中的一个重要因素，促成最终的神经元功能障碍和死亡。
