Cerebrospinal Fluid Markers Of Aging And Brain Disease

衰老和脑疾病的脑脊液标志物

• 批准号: 6667885
• 负责人: Stanley I. Rapoport
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 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/6667885
• 关键词: Alzheimer's disease; aging; aluminum; biomarker; blood brain barrier; brain disorder diagnosis; calcium ion; cerebrospinal fluid; diagnosis design /evaluation; enzyme linked immunosorbent assay; human tissue; phosphoproteins; phosphorylation; tau proteins

(1) Alzheimer disease (AD) is associated with accumulation of hyperphosphorylated tau protein within paired helical filaments of brain neurons. An immunologic ELISA assay was developed to measure the cerebrospinal fluid (CSF) concentration of tau protein phosphorylated at threonine 231. AD could be accurately diagnosed and its course followed with high specificity and selectivity by measuring phosphorylated tau in CSF. (2) Cultured PC12 cells were exposed to 0.1-100 micromole aluminum chloride for 6 hours. Northern blot analyses showed that the mRNA level of a subunit of cytochrome c oxidase, an enzyme in the mitochondrial electron transport chain, was reduced by 70% after exposure to only 1 micromole aluminum. This low concentration is found in postmortem brain from patients with AD and dialysis dementia, suggesting a toxic role for aluminum in these disorders. (3) Osmotic opening of the blood-brain barrier by intracarotid infusion of a hypertonic sugar solution is used clinically to treat malignant brain tumors and to grant access to brain of drugs and proteins in animal models. Opening involves the widening of tight junctions between vascular endothelial cells. Opening is mediated by increased intracellular Ca2+ and contraction of the endothelial cytoskeleton. Opening is prolonged in rats pretreated with a Na+/Ca2+ exchange blocker.

（1）阿尔茨海默氏病（AD）与脑神经元成对的螺旋丝中的高磷酸化tau蛋白的积累有关。开发了一种免疫ELISA分析，以测量在三氨酸231上磷酸化的tau蛋白的脑脊液浓度。可以准确诊断为AD，并通过测量CSF中的磷酸化tau来准确地诊断出其课程，其过程之后具有高特异性和选择性。 （2）将培养的PC12细胞暴露于0.1-100微米氯化物6小时。 Northern印迹分析表明，细胞色素C氧化酶的亚基的mRNA水平是线粒体电子传输链中的一种酶，仅暴露于1个微摩尔铝后，降低了70％。这种低浓度是在AD和透析痴呆症患者的死后大脑中发现的，这表明铝在这些疾病中的有毒作用。 （3）通过腹膜内输注高渗糖溶液对血脑屏障的渗透开放临床治疗恶性脑肿瘤，并允许动物模型中药物和蛋白质的大脑访问。开口涉及血管内皮细胞之间紧密连接的扩大。开口是由细胞内Ca2+增加和内皮细胞骨架的收缩介导的。开口在用Na+/Ca2+交换阻滞剂预处理的大鼠中延长。