CLINICAL TRIAL: EVALUATION OF THE SAFETY, TOLERABILITY AND IMPACT ON BIOMARKERS

临床试验：评估安全性、耐受性和对生物标志物的影响

• 批准号: 7725024
• 负责人: RUTH MULNARD MCCARGAR
• 金额: $ 0.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725024
• 关键词: Acetylcholinesterase Inhibitors; Activities of Daily Living; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Brain; Cognitive; Computer Retrieval of Information on Scientific Projects Database; Degenerative Disorder; Dementia; Deposition; Disease; Elderly; Etiology; Facilities and Administrative Costs; Funding; Grant; Institution; Lead; Life Expectancy; Link; Memantine; Memory Loss; Nerve Degeneration; Neurons; Neurotransmitters; Public Health; Research; Research Personnel; Resources; Source; System; Thinking; Toxic effect; United States National Institutes of Health; prevent

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alzheimer's Disease (AD), a progressive degenerative disease of the brain resulting in impaired memory and loss of cognitive and functional abilities, is the most common cause of dementia in the elderly. It poses a huge public health problem, particularly as life expectancy continues to increase. In the US, the direct and indirect costs of AD were estimated at over $100 billion per year (Ernst 1994). Currently approved treatment for AD includes acetylcholinesterase inhibitors and memantine, both of which target neurotransmitter systems and show symptomatic benefits. There is no disease-modifying treatment to prevent AD or to slow its progression. A major hypothesis about the etiology of AD is that beta-amyloid (A?) aggregates and is deposited in the brain, which leads to neuronal damage and ultimately to AD (reviewed in Hardy 1997). A? ending at residue 42 (A?42) is thought to be the key initiator because A?42 predominates in early amyloid deposits in the brain and has a greater propensity to aggregate, form fibrils, and lead to cellular toxicity than A? ending at residue 40 (A?40) or shorter forms of A?. Oxidative damage is a key factor implicated in the neurodegeneration of AD (Behl 1999) and can be linked to A? (Pratico 1999, Lustbader 2004).

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 阿尔茨海默氏病（AD）是大脑的进行性退行性疾病，导致记忆力受损，认知和功能能力的丧失是老年痴呆症的最常见原因。它带来了一个巨大的公共卫生问题，尤其是随着预期寿命的持续增加。在美国，AD的直接和间接费用估计为每年超过1000亿美元（Ernst 1994）。目前对AD的批准治疗包括乙酰胆碱酯酶抑制剂和美金刚蛋白，它们均靶向神经递质系统并显示出症状的好处。没有改善疾病的治疗方法可以防止AD或减缓其进展。关于AD病因的一个主要假设是β-淀粉样蛋白（A？）聚集体并沉积在大脑中，这会导致神经元损害并最终导致AD（在Hardy 1997中进行了综述）。一个？以残基42（A？42）结尾，被认为是关键的引发剂，因为A？42在大脑早期的淀粉样蛋白沉积物中占主导地位，并且比A更大的倾向，形成原纤维并导致细胞毒性比A？以残留物40（A？40）或较短的A？结尾。氧化损伤是关键因素与AD的神经变性有关（Behl 1999），并且可以与A相关。 （Pratico 1999，Lustbader 2004）。