BACKGROUND Various methodologies have been employed for the localization of amyloid plaques in numerous studies on Alzheimer's disease. The majority of these stains are thought to label the plaques by virtue of their affinity for aggregated Aβ. However, plaques are known to contain numerous other components, including multivalent metals such as zinc. OBJECTIVE This investigates whether it is possible to localize the presence of zinc in parenchymal and vascular amyloid plaques in afflicted brains. To accomplish this, a novel fluorescent zinc chelator, HQO, was investigated to determine its mechanism of binding and to optimize a stain for the high contrast and resolution histological localization of amyloid plaques. METHODS A novel zinc chelator, HQ-O, was developed for localizing zinc within amyloid plaques. The histology involves incubating tissue sections in a dilute aqueous solution of HQ-O. Its compatibility with a variety of other fluorescent methodologies is described. RESULTS All amyloid plaques are stained in fine detail and appear bright green under blue light excitation. The staining of parenchymal plaques correlates closely with that seen following staining with antibodies to Aβ, however, the HQ-O sometimes also label additional globular structures within blood vessels. In situ mechanistic studies revealed that fluorescent plaque-like structures are only observed with HQ-O when synthetic Aβx-42 is aggregated in the presence of zinc. CONCLUSION Zinc is intimately bound to all amyloid plaques, which was demonstrated by its histological localization using a novel fluorescent zinc chelator, HQ-O. Additionally, the tracer is also capable of labeling intravascular leucocytes due to their high zinc content.

中文翻译：

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锌螯合剂HQ-O对APP-PS1小鼠和患有阿尔茨海默氏病的人类组织切片中淀粉样斑块的高对比度和分辨率标记：实际和理论上的考虑。

背景技术在关于阿尔茨海默氏病的许多研究中，已经采用了各种方法来定位淀粉样蛋白斑块。这些污渍中的大多数被认为是由于斑块对聚集的Aβ的亲和力而标记了斑块。但是，已知斑块包含许多其他成分，包括多价金属，例如锌。目的研究是否可以在患病的大脑的实质和血管淀粉样斑块中定位锌的存在。为此，研究了一种新型的荧光锌螯合剂HQO，以确定其结合机理并优化了淀粉样斑块的高对比度和分辨率组织学定位的染色剂。方法开发了一种新型的锌螯合剂HQ-O，用于在淀粉样斑块中定位锌。组织学包括将组织切片在HQ-O的稀水溶液中孵育。描述了其与多种其他荧光方法的兼容性。结果所有淀粉样蛋白斑块均被细微染色，在蓝光激发下呈亮绿色。实质斑块的染色与抗Aβ抗体染色后的染色密切相关，但是，HQ-O有时还会标记血管内的其他球状结构。原位机理研究表明，只有在锌存在下合成Aβx-42聚集时，HQ-O才能观察到荧光斑块状结构。结论锌与所有淀粉样蛋白斑块紧密结合，这是通过使用新型荧光锌螯合剂HQ-O的组织学定位证明的。另外，