ALUMINUM IN ALZHEIMER'S DISEASE

铝在阿尔茨海默病中的作用

• 批准号: 5204102
• 负责人: C R SWYT
• 金额: --
• 依托单位: NATIONAL CENTER FOR RESEARCH RESOURCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5204102
• 关键词: Alzheimer's disease; aluminum; cryopreservation; fluorescence microscopy; human tissue; iron; neuritic plaques; neurofibrillary tangles; pathologic process; phosphorus; stainings; sulfur

The role of aluminum in the etiology of Alzheimer's disease remains controversial because of the contradictory results reported by the many laboratories in the field. Many of the laboratories relied on fixatives and stains to facilitate the unambiguous identification of plaques and neurofibrillary tangles (NFTs), the indicators of the disease. However, the chemical processes of fixing and staining compromise the distributions and concentrations of aluminum and other elements of interest. Measurements on unfixed, unstained sections in which elemental distributions are assumed to be preserved are questioned because the identification of the structures being measured is difficult. A methodology has been developed that permits the unambiguous identification of plaques and NFTs in unfixed, unstained sections, that does not alter the elemental distributions, and that provides detectability and rapid imaging of the aluminum distribution at concentrations in the ppm range. This methodology uses thioflavin-stained sections for observation by fluorescent LM, and freeze-dried cryosections for observation by backscattered-electron imaging (BSI) and for quantitative measurement by electron-induced X-ray micro-analysis and SIMS. No aluminum above the normal background concen-tration has been observed in tangled neurons in sections prepared by this method. However, a marked increase in sulphur relative to phosphorus has been observed in NFTs, and of Fe in plaques.

铝在阿尔茨海默病病因中的作用仍然存在 有争议的是，因为 该领域的许多实验室。许多实验室依赖于 固定剂和着色剂，以便于明确识别 斑块和神经原纤维缠结(NFTs)是 疾病。然而，固定和染色的化学过程 危害铝和其他物质的分布和浓度 感兴趣的元素。对未固定、未染色的切片的测量 假设元素分布保持不变的是 质疑是因为被测量的结构的识别 是很困难的。已经开发出一种方法，允许 未固定、未染色的斑块和NFT的明确识别 部分，这不会改变元素分布，并且 提供铝分布的可探测性和快速成像 浓度在ppm范围内。此方法使用 硫代黄素染色切片用于荧光光镜观察，以及 用背散射电子显微镜观察冷冻干燥切片 成像(BSI)和电子诱导定量测量 X射线显微分析和SIMS。无铝超标 背景：在交织在一起的神经元中观察到浓度升高。 用这种方法制作的切片。然而，明显增加的是 在NFTs中观察到硫相对于磷，在NFTs中观察到Fe 斑块。