Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer's disease
Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer's disease
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DOI：
10.1016/s0006-8993(00)03075-4
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发表时间：
2001-01-12
期刊：
影响因子：
2.9
通讯作者：
Makita, Z
中科院分区：
文献类型：
--
作者：
Sasaki, N;Toki, S;Makita, Z
晚期糖基化终产物（AGE）和AGE受体（RAGE）与糖尿病（DM）的慢性并发症有关，并在阿尔茨海默病（AD）的发病机制中发挥重要作用。在本研究中，我们建立了一种多克隆抗RAGE抗体，并检测了AD和DM患者神经元和星形胶质细胞中淀粉样蛋白β (a β)、AGE和RAGE的免疫组织化学定位。我们的抗RAGE抗体识别了人脑组织中全长RAGE （50 kd）和n端RAGE （35 kd）。所有受试者海马神经元核周（尤其是CA3和CA4）均有β -、AGE-和rage阳性颗粒。这些免疫阳性颗粒的分布和染色模式与各抗体具有良好的一致性。在AD中，大多数星形胶质细胞同时含有age和rage阳性颗粒，其分布几乎相同。β -阳性颗粒不太常见，但β -、AGE-和rage -阳性颗粒可在单个星形胶质细胞的一部分共定位。在DM患者和对照病例中，age和rage阳性星形胶质细胞非常罕见。这些发现支持了糖基化AP在星形胶质细胞中通过RAGE摄取并通过溶酶体途径降解的假设。除了AGE的存在外，AGE的降解过程和受体介导的反应也可能导致神经元功能障碍，促进AD的进展。(C) 2001 Elsevier Science B.V.版权所有
Advanced glycation end products (AGE) and the receptor for AGE (RAGE) have been implicated in the chronic complications of diabetes mellitus (DM), and have been reported to play an important role in the pathogenesis of Alzheimer's disease (AD). In this study, we established a polyclonal anti-RAGE antibody, and examined the immunohistochemical localization of amyloid beta protein (A beta), AGE, and RAGE in neurons and astrocytes from patients with AD and DM. Our anti-RAGE antibody recognized full-length RAGE (50 kd) and N-terminal RAGE (35 kd) in human brain tissue. A beta-, AGE-, and RAGE-positive granules were identified in the perikaryon of hippocampal neurons (especially from CA3 and CA4) in all subjects. The distribution and staining pattern of these immunopositive granules showed good concordance with each antibody. In AD, most astrocytes contained both AGE-and RAGE-positive granules and their distribution was almost the same. A beta -positive granules were less common, but A beta-, AGE-, and RAGE-positive granules were colocalized in one part of a single astrocyte. In DM patients and control cases, AGE-and RAGE-positive astrocytes were very rare. These finding support the hypothesis that glycated AP is taken up via RAGE and is degraded through the lysosomal pathway in astrocytes. In addition to the presence of AGE, the process of AGE degradation and receptor-mediated reactions may contribute to neuronal dysfunction and promote the progression of AD.(C) 2001 Elsevier Science B.V. All rights reserved.