Hippocampal RAGE immunoreactivity in early and advanced Alzheimer's disease.
Hippocampal RAGE immunoreactivity in early and advanced Alzheimer's disease.
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DOI：
10.1016/j.brainres.2008.06.124
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发表时间：
2008-09-16
期刊：
影响因子：
2.9
通讯作者：
Stopa, Edward G.
中科院分区：
文献类型：
--
作者：
Miller, Miles C.;Tavares, Rosemarie;Johanson, Conrad E.;Hovanesian, Virginia;Donahue, John E.;Gonzalez, Liliana;Silverberg, Gerald D.;Stopa, Edward G.
微血管积聚和神经元淀粉样蛋白β肽（Aβ）的过量产生是阿尔茨海默病（AD）的病理特征。在这项研究中，我们检测了晚期糖基化终产物受体（RAGE），这是一种多配体受体，存在于神经元和大脑微血管内皮中，与a β结合。在老年对照组（n=6）、早期AD样病理患者（n=6）和严重的Braak V-VI AD患者（n=6）中评估RAGE表达。用针对RAGE的特异性多克隆抗体对人海马进行染色（Research Diagnostics, Flanders， NJ）。免疫反应性局限于神经元和脑内皮细胞。对灰度图像进行定量图像分析，评估脑微血管（5 ~ 20 μm）横截面内皮RAGE免疫反应产物的总表面积。通过将RAGE分别与CD-31和神经丝偶联获得共聚焦图像，以确认RAGE在微血管和神经元中的免疫反应性。与老年对照相比（p<0.001），与早期AD病理患者相比（p=0.0125），严重Braak V-VI AD患者内皮细胞RAGE免疫反应性显著增加。此外，当将未报告AD病理的老年对照组与早期AD样病理患者进行比较时，内皮细胞RAGE免疫反应性显著增加（p=0.038）。我们的数据表明，微血管RAGE水平随着AD的发病而增加，并随着AD病理严重程度的增加而线性增加（p<0.0001）。
Microvascular accumulation and neuronal overproduction of amyloid-β peptide (Aβ) are pathologic features of Alzheimer’s disease (AD). In this study, we examined the receptor for advanced glycation endproducts (RAGE), a multi-ligand receptor found in both neurons and cerebral microvascular endothelia that binds Aβ. RAGE expression was assessed in aged controls (n=6), patients with early AD-like pathology (n=6), and severe, Braak V-VI AD (n=6). Human hippocampi were stained with a specific polyclonal antibody directed against RAGE (Research Diagnostics, Flanders, NJ). Immunoreactivity was localized in both neurons and cerebral endothelial cells. Quantitative image-analyses were performed on grayscale images to assess the total surface area of endothelial RAGE immunoreaction product in cross sections of cerebral microvessels (5–20 μm). Confocal images were acquired for confirmation of RAGE immunoreactivity in both microvessels and neurons by coupling RAGE with CD-31 and neurofilament, respectively. A significant increase in endothelial RAGE immunoreactivity was found in severe Braak V-VI AD patients when compared to aged controls (p<0.001), and when compared to patients with early AD pathology (p=0.0125). In addition, a significant increase in endothelial RAGE immunoreactivity was witnessed when comparing aged controls having no reported AD pathology with patients having early AD-like pathology (p=0.038). Our data suggest that microvascular RAGE levels increase in conjunction with the onset of AD, and continue to increase linearly as a function of AD pathologic severity (p<0.0001).
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影响因子：
82.9
作者：
Deane, R;Yan, SD;Zlokovic, B
通讯作者：
Zlokovic, B
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3.2
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Schnell, SA;Staines, WA;Wessendorf, MW
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Wessendorf, MW
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Leclerc, Estelle;Fritz, Gunter;Galichet, Arnaud
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Galichet, Arnaud
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2.9
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Makita, Z
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Silverberg, GD;Heit, G;Saul, TA
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