INJURY RESPONSES IN ALZHEIMER DISEASE AND OTHER HUMAN CONDITIONS

阿尔茨海默病和其他人类疾病的损伤反应

• 批准号: 6267636
• 负责人: Sue Tilton Griffin
• 金额: $ 1.67万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6267636
• 关键词: Alzheimer's disease; amyloid proteins; amyloidosis; apolipoproteins; astrocytes; cellular pathology; coronary artery; coronary disorder; gene expression; glia; head /neck injury; human genetic material tag; human tissue; immunocytochemistry; interleukin 1; messenger RNA; microglia; molecular pathology; neural degeneration; neuritic plaques; neurofibrillary tangles; neurotrophic factors; partial seizure; pathologic process; temporal lobe /cortex disorder

The objective of Project One is to address the idea that overexpression of glia-derived cytokines, especially interleukin-1 (IL-1), is a seminal event in the pathogenesis of Alzheimer's disease (AD), giving rise to a two-armed cascade of cellular and molecular events that lead to neuron cell dysfunctions, including accumulation of neurofibrillary tangles and overgrowth of neurites, and eventually death which induces further overexpression of IL-1 in what becomes then a self-propagating "system" or cascade. In AD, we seek evidence of the involvement of cascade-related cellular and molecular events in the presumed neuropathological progression that accounts for the progressive nature of the dementia by determining their interrelationships with regard to: (i) specific plaque types and (ii) the recognized regional distribution of neuropathological changes in AD. In head injury, a recently established risk factor for later development of AD, we can know the time and age at onset, severity, and clinical course and thus relate these parameters to the distribution of plaques according to type within as well as across brain regions. In non-demented critical coronary artery disease (cCAD) patients where significant AD-like neuropathological changes have been observed, we seek to clarify the relationship of these changes to AD as we: (i) compare their regional distribution to that in AD and (ii) assess the potential involvement of cascade-related cellular and molecular events in specific plaque types within and across brain regions. In refractory temporal epilepsy, where we have evidence that some cascade-related cellular and molecular events occur, we seek to: (i) evaluate spatial relationships between defined epileptogenic foci and these events and (ii) compare these with those occurring in AD, head injury, and cCAD. A number of molecular techniques routine to our laboratory will be used to address our specific aims, which at successful completion will provide information regarding the generalizability of our proposed cascade--a necessity if it is to be useful in developing rational therapeutic strategies.

项目的目的是解决过表达的想法 胶质衍生的细胞因子，尤其是白介素-1（IL-1），是一个精液 阿尔茨海默氏病（AD）发病机理中的事件，引起了 导致神经元的细胞和分子事件的两臂级联 细胞功能障碍，包括神经原纤维缠结和 神经突的过度生长，最终导致死亡进一步诱导 IL-1的过表达在当时自我传播的“系统”中 或级联。 在AD中，我们寻求证据表明与级联相关的细胞参与 和分子事件在假定的神经病理学进展中 通过确定痴呆症的渐进性 关于：（i）特定斑块类型和（ii）的相互关系 公认的AD神经病理变化的区域分布。 在头部受伤中，最近确定的后期发展风险因素 在AD上，我们可以知道发病，严重性和临床时的时间和年龄 课程，从而将这些参数与斑块的分布联系起来 根据内部和整个大脑区域的类型。 在非痴呆的关键冠状动脉疾病（CC​​AD）患者中 已经观察到了重大的广告样神经病理学变化，我们寻求 为了阐明这些变化与我们一样的关系：（i）比较 它们在AD中的区域分布和（ii）评估潜力 级联相关的细胞和分子事件参与特定 大脑区域内和跨区域的斑块类型。 在耐火性时间癫痫中，我们有证据表明有些 与级联相关的细胞和分子事件发生，我们寻求：（i） 评估定义的癫痫灶和 这些事件和（ii）将它们与AD中发生的事件进行比较，头部 受伤和CCAD。 将使用许多分子技术对我们的实验室使用 解决我们的特定目标，成功完成将提供 有关我们提议的级联的普遍性的信息 - 必要性，如果要在开发理性治疗方面有用 策略。