ALZHEIMER'S DISEASE CENTER CORE GRANT

阿尔茨海默病中心核心拨款

• 批准号: 3100938
• 负责人: EARL ZIMMERMAN
• 金额: $ 50.44万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-07-06 至 1995-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3100938
• 关键词: Alzheimer's disease

dementia has reached epidemic proportions in our aging society, and most affected are thought to have Alzheimer's Disease (AD). Clinical diagnostic accuracy is only about 80% and neuropathological diagnosis presents some difficulty. The cause of D is unknown. It is suspected that AD is heterogeneous. There are also overlaps of AD with Parkinson's disease and vascular dementia. The objectives of this proposal are to apply objective clinical measures to more accurately diagnose AD and to follow these patients and controls in a longitudinal study. Clinical data will be correlated with neuropathological analysis. A patient data base (patient registry) and tissue repository (brain bank) will support these studies. Three major clinical research projects concern heterogeneity: one will assess the extrapyramidal subtype using clinical, electrophysiological and biochemical measures; a related pilot project assesses postural control and vestibular function measures as diagnostic tools for this subtype and another pilot explores new probes for dopamine-2 receptors as another biochemical tool. Another major clinical project investigates genetic heterogeneity by HLA markers. The third clinical project applies hemorheological methods to study the role of the cerebral circulation in AD and vascular dementia. These research efforts are aimed at better understanding different patient populations with subtypes of AD and the different factors which may contribute to the cause. Both clinical and biochemical markers may therefore not only provide a better means of diagnosis but may eventually result in understanding etiology and therapy. Another pilot is aimed at developing better immunochemical probes for beta-amyloid which may be useful in diagnosis and for assessing the potential existence of abnormal forms of the protein in AD as a possible basic mechanism in causality. Another pilot, purely basic in design, examines the role of glutamine in memory mechanisms in the rat hippocampus by studying the influence of cholinergic inputs on excitatory synaptic transmission in dissociated cultures of hippocampus with voltage and patch clamp techniques. In addition to the above, a beginning is made to study possible ameliorative therapies in a pilot project which evaluates bright light or melatonin administration as possible treatment for disturbance in sleep/wake cycles in AD. There is also a therapeutic feasibility trial using synvinolin (an analog of lovastatin which lowers cholesterol) in AD and vascular dementia who have rheological abnormalities.

痴呆症在我们老龄化的社会中达到了流行病，大多数 被认为患有阿尔茨海默氏病（AD）。 临床 诊断准确性仅为80％，神经病理学诊断 带来一些困难。 D的原因是未知的。 怀疑 该广告是异质的。 帕金森的广告也有重叠 疾病和血管痴呆。 该提议的目标是 采用客观的临床指标更准确地诊断AD，并 在一项纵向研究中关注这些患者和对照。 临床数据 将与神经病理学分析相关。 患者数据库 （患者注册表）和组织存储库（脑库）将支持这些 研究。 三个主要的临床研究项目涉及异质性：一个将会 使用临床，电生理和 生化措施；相关的试点项目评估姿势控制 和前庭功能措施作为该亚型的诊断工具， 另一个飞行员探索了多巴胺-2受体作为另一种的新探针 生化工具。 另一个主要的临床项目研究了遗传 HLA标记的异质性。 第三个临床项目适用 研究大脑循环作用在 AD和血管痴呆。 这些研究工作旨在更好 通过AD的亚型了解不同的患者人群 可能导致原因的不同因素。 临床和 因此，生化标志物不仅可以提供更好的手段 诊断但最终可能导致理解病因和治疗。 另一个飞行员旨在为更好的免疫化学探针开发 β-淀粉样蛋白可能可用于诊断和评估 AD中蛋白质异常形式的潜在存在 因果关系的基本机制。 另一个飞行员，纯粹的设计基础， 检查谷氨酰胺在大鼠海马中的记忆机制中的作用 通过研究胆碱能输入对兴奋性突触的影响 用电压和斑块的海马分离培养物传播 夹具技术。 除上述内容外，还开始学习 试点项目中的改善疗法，该疗法评估明亮的光或 褪黑激素给药作为干扰的可能治疗 在广告中睡觉/唤醒周期。 也有一项治疗性可行性试验 在AD中使用Synvinolin（一种降低胆固醇的Lovastatin的类似物） 和具有流变学异常的血管痴呆。