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)阿尔茨海默病（AD）与脑神经元的成对螺旋丝内过度磷酸化的tau蛋白的积累有关。开发了免疫学ELISA测定法来测量在苏氨酸231处磷酸化的tau蛋白的脑脊液（CSF）浓度。通过检测脑脊液中磷酸化tau蛋白的含量，可以准确诊断AD，并具有高度的特异性和选择性。(2)将培养的PC 12细胞暴露于0.1-100微摩尔氯化铝6小时。北方印迹分析表明，细胞色素c氧化酶的一个亚基的mRNA水平，在线粒体电子传递链的酶，减少了70%后，暴露于只有1微摩尔铝。在AD和透析性痴呆患者的死后大脑中发现了这种低浓度，表明铝在这些疾病中具有毒性作用。(3)通过颈动脉内输注高渗糖溶液渗透打开血脑屏障在临床上用于治疗恶性脑肿瘤，并在动物模型中允许药物和蛋白质进入脑。开放涉及血管内皮细胞之间紧密连接的加宽。开放是由细胞内Ca 2+增加和内皮细胞骨架收缩介导的。在用Na+/Ca 2+交换阻滞剂预处理的大鼠中，开放延长。