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一种用于淀粉样蛋白沉积物鉴定和定量元素分析的新方法——对阿尔茨海默病病理学的见解。

A novel approach to the identification and quantitative elemental analysis of amyloid deposits--insights into the pathology of Alzheimer's disease.

作者信息

Rajendran Reshmi, Minqin Ren, Ynsa Maria Dolores, Casadesus Gemma, Smith Mark A, Perry George, Halliwell Barry, Watt Frank

机构信息

Centre for Ion Beam Applications, Department of Physics, Blk S 12, Faculty of Science, National University of Singapore, 2, Science Drive 3, Singapore 117542, Singapore.

出版信息

Biochem Biophys Res Commun. 2009 Apr 24;382(1):91-5. doi: 10.1016/j.bbrc.2009.02.136. Epub 2009 Mar 1.

DOI:10.1016/j.bbrc.2009.02.136
PMID:19258010
Abstract

There is considerable interest in the role of metals such as iron, copper, and zinc in amyloid plaque formation in Alzheimer's disease. However to convincingly establish their presence in plaques in vivo, a sensitive technique is required that is both quantitatively accurate and avoids isolation of plaques or staining/fixing brain tissue, since these processes introduce contaminants and redistribute elements within the tissue. Combining the three ion beam techniques of scanning transmission ion microscopy, Rutherford back scattering spectrometry and particle induced X-ray emission in conjunction with a high energy (MeV) proton microprobe we have imaged plaques in freeze-dried unstained brain sections from CRND-8 mice, and simultaneously quantified iron, copper, and zinc. Our results show increased metal concentrations within the amyloid plaques compared with the surrounding tissue: iron (85 ppm compared with 42 ppm), copper (16 ppm compared to 6 ppm), and zinc (87 ppm compared to 34 ppm).

摘要

铁、铜和锌等金属在阿尔茨海默病淀粉样斑块形成中的作用备受关注。然而,要令人信服地确定它们在体内斑块中的存在,需要一种敏感的技术,该技术既要定量准确,又要避免斑块的分离或脑组织的染色/固定,因为这些过程会引入污染物并使组织内的元素重新分布。结合扫描透射离子显微镜、卢瑟福背散射光谱法和粒子诱导X射线发射这三种离子束技术,并与高能(MeV)质子微探针联用,我们对来自CRND-8小鼠的冻干未染色脑切片中的斑块进行了成像,并同时对铁、铜和锌进行了定量。我们的结果显示,与周围组织相比,淀粉样斑块中的金属浓度增加:铁(分别为85 ppm和42 ppm)、铜(分别为16 ppm和6 ppm)和锌(分别为87 ppm和34 ppm)。

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