TRACE ELEMENTS IN AGED NEURONS AND SENILE DEMEMTIA

老年神经元和老年痴呆症中的微量元素

• 批准号: 3117905
• 负责人: Daniel P Perl
• 金额: $ 18.98万
• 依托单位: MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3117905
• 关键词: Alzheimer's disease; Parkinson's disease; adult human (21+); aging; aluminum; atomic absorption spectrometry; brain metabolism; central nervous system disorders; electron microscopy; electron probe spectrometry; ethnic group; hippocampus; human ecology; human tissue; interneurons; mature animal; nervous system disorder epidemiology; neural degeneration; neurochemistry; neurofibrillary tangles; neurofilament; postmortem; scanning electron microscopy; southeast Asia; tissue /cell preparation; trace elements

Senile dementia, Alzheimer's type (SDAT) is one of the most common, yet most poorly understood of neurologic disorders. The principle neuropathologic lesion encountered in the brains of patients with SDAT is theneurofibrillary tangle (NFT). Recent studies have pointed to the possible role of excess aluminum in the pathogenesis of SDAT. Using scanning electron microscopy in conjunction with electron probe analysis, we have developed techniques for the determination of intraneuronal trace element analysis. Using these techniques we have identified intraneuronal accumulations of aluminum within neurofibrillary tangle-bearing cells in the hippocampus and frontal cortex of patients with SDAT. With this as a basis, we have begun to study the intraneuronal trace element composition of brain specimens derived from the Chamorros of Guam. The Chamorros are a people characterized by a striking propensity to extensive NFT formation. This tendency among the Chamorros is also accompanied by an exceedingly high incidence of ALS and Parkinsonism with severe dementia (PD). Preliminary data indicate that tangle-bearing hippocampal neurons in these cases also demonstrate significant aluminum accumulations. Epidemiologic evidence suggests that these intracellular accumulations are associated with local environmental factors on Guam related to water and soil conditions. We intend to collect a series of brain tissue samples of Guananian ALS and PD cases and non-impaired controls, as well as a comparable series of ALS, idiopathic Parkinsonism and SDAT cases and normal controls from the mainland U.S. Intracellular trace element analysis will be performed on neurons within the hippocampus, cortex, and the motor and extraphyramidal systems. Sensitive quantitative measures of tissue levels of several trace elements also will be obtained by atomic absorption spectrometry. These data will provide a means to evaluate the possible role of neurotoxic trace element accumulations in NFT formation, motor neuron and extrapyramidal system degeneration. By analysis of the clinical, metabolic and epidemiologic data avaiable from these cases, we will evaluate potential sources for these element abnormalities.

老年痴呆症，阿尔茨海默氏症类型（SDAT）是最常见的一种，但是 对神经系统疾病的了解最差。 原则 SDAT患者的大脑遇到的神经病理病变是 theneurofirillary Tangle（NFT）。 最近的研究指出 多余铝在SDAT发病机理中的可能作用。 使用 扫描电子显微镜与电子探针分析结合使用， 我们已经开发了确定神经内神经元痕迹的技术 元素分析。 使用这些技术，我们已经确定了神经内神经元 铝在神经纤维缠结细胞中的积累 SDAT患者的海马和额叶皮层。 以此为 基础，我们已经开始研究神经元痕量元件组成 源自关岛的Chamorros的脑标本。 Chamorros是一个 人们以惊人的NFT形成倾向的人。 Chamorros中的这种趋势也伴随着 严重痴呆（PD）的ALS和帕金森主义的高发病率。 初步数据表明在这些数据中是否有缠结的海马神经元 病例还显示出明显的铝积累。 流行病学 有证据表明这些细胞内积累是相关的 关岛与水和土壤有关的当地环境因素 状况。 我们打算收集一系列的脑组织样品 圭亚那ALS和PD案例以及未受损的控件以及 可比较的ALS，特发性帕金森主义和SDAT病例和正常 来自美国大陆的细胞内痕量元素分析的控制将 可以在海马，皮质和电动机内的神经元上进行 跨锥体系统。 组织水平的敏感定量测量 还将通过原子吸收获得几个痕量元素 光谱法。 这些数据将提供一种评估可能的方法 神经毒性痕量元素在NFT形成，运动中的作用 神经元和锥体外系统变性。 通过分析 可以从这些情况下避免使用临床，代谢和流行病学数据，我们 将评估这些元素异常的潜在来源。