Assessment of Biomarkers and Behavior in a Transgenic Rat Model of AD

AD 转基因大鼠模型的生物标志物和行为评估

• 批准号: 7922082
• 负责人: Edmond Huatung Teng
• 金额: $ 10.8万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7922082
• 关键词: Achievement; Address; Affect; Aftercare; Age; Age-Months; Alzheimer' s Disease; Alzheimer' s disease model; Amyloid beta-Protein; Animal Model; Animals; Automobile Driving; Behavior; Behavioral; Binding; Biochemical; Biochemical Markers; Biological Markers; Biological Markers; Biological Models; Cerebrospinal Fluid; Characteristics; Chronic; Clinical Pharmacology; Clinical Trials; Cognitive; Complement; Curcumin; Data; Dementia; Deposition; Developed Countries; Development; Development Plans; Disease; Disease Progression; Docosahexaenoic Acids; Elderly; Exhibits; Expenditure; Future; Goals; Healthcare Systems; High Prevalence; Human; Image; Individual; Intervention; Investigation; Laboratories; Los Angeles; Measurement; Measures; Memory; Memory impairment; Methodology; Methods; Modeling; Molecular Probes; Mus; Outcome Measure; Patients; Performance; Pharmaceutical Preparations; Population; Positron-Emission Tomography; Prevalence; Principal Investigator; Rattus; Relative (related person); Research; Research Project Grants; Role; Sample Size; Severity of illness; Staging; Surrogate Endpoint; Synapses; Technical Expertise; Therapeutic; Therapeutic Agents; Time; Transgenic Mice; Transgenic Organisms; Translational Research; Treatment Efficacy; United States; Veterans; age related; base; behavior test; brain tissue; career; career development; clinically relevant; cost; dietary supplements; drug discovery; follow-up; hyperphosphorylated tau; in vivo; mouse model; neuropathology; novel; novel therapeutics; primary outcome; programs; response; skills; tau Proteins; tau-1; therapy duration; treatment duration; treatment effect

DESCRIPTION (provided by applicant): My prior research background has involved the assessment of cognitive, behavioral and functional deficits associated with memory impairment in both animal models and human populations. My current and long- term career goals are focused upon developing a translational research program that uses biochemical markers to accelerate the discovery of new therapies for Alzheimer's disease (AD). The career development plan described in this application will facilitate my achievement of these goals by allowing me to obtain greater technical expertise with the biochemical and pharmacological aspects of AD through the acquisition of new research skills in the laboratory of Dr. Gregory Cole at the Greater Los Angeles Veterans Affairs Healthcare System, and a more comprehensive understanding of the AD drug discovery through the completion of formal coursework in clinical pharmacology and clinical trials methodology at UCLA. This career development plan will be complemented by the proposed research project, which seeks to determine whether an transgenic rat model of AD can be used to determine the utility of longitudinal measurements of two potential biological markers of AD in the cerebrospinal fluid (CSF), beta-amyloid 1-42 (AP42) and phosphorylated tau (p-tau) for the assessment of disease progression and response to treatment at early stages of the disease. We hypothesize that the levels of these markers will change in conjunction with age- associated increases in disease progression. We further hypothesize that these changes will be differentially modulated by treatment with curcumin or docosahexaenoic acid (DMA) and will be affected by both the duration of treatment and the severity of disease at the time of treatment. The use of curcumin and DHA, which have demonstrated efficacy in reducing disease progression in other animal models and have distinct underlying mechanisms, will allow us to assess how successful therapies affect these putative CSF biomarkers of AD. The results of this study will clarify the roles of CSF Ap42 and p-tau in clinical trials of AD therapeutics and form the basis for future studies of other potential CSF biomarkers and other potential therapeutic treatments in this promising animal model system. RELEVANCE: This project has the potential to help develop more efficient methods for identifying promising medications for AD that result in clinical trials that take less time and money to complete. Facilitating the development of more effective medications for AD is of critical importance to the NIA given the elevated prevalence of this disease in the rapidly growing elderly populations of the United States and other industrialized countries.

描述（由申请人提供）：我先前的研究背景涉及对动物模型和人类种群中记忆障碍相关的认知，行为和功能缺陷的评估。我目前和长期的职业目标集中在制定一项翻译研究计划上，该计划使用生化标记来加速对阿尔茨海默氏病（AD）的新疗法的发现。本申请中描述的职业发展计划将通过使Gregory Cole博士在大洛杉矶退伍军人事务医疗系统的Gregory Cole博士的实验室中获得新的研究技能，通过获得新的研究技能来获得AD的生物化学和药理学方面，从而有助于我实现这些目标，并通过对AD Prunical进行了全面的方法，该方法在广泛的临床药物过程中获得了更全面的了解。拟议的研究项目将补充这项职业发展计划，该项目旨在确定AD的转基因大鼠模型是否可用于确定在脑脊液（CSF），β-淀粉样蛋白1-42（AP42）和phosphorated Tau（P-Tau）疾病（beta-Amyloid）中的纵向测量的实用性，以确定AD的纵向测量模型（CSF）的脑脊液（CSF）效用（PASF）。 疾病。我们假设这些标记的水平将随着年龄相关的疾病进展增加而变化。我们进一步假设，这些变化将通过姜黄素或二十二碳六烯酸（DMA）的治疗来差异调节，并将受到治疗持续时间和治疗时疾病严重程度的影响。姜黄素和DHA的使用在降低其他动物模型中疾病进展方面有效并具有不同的潜在机制，这将使我们能够评估成功疗法如何影响这些推定的AD的CSF生物标志物。这项研究的结果将阐明CSF AP42和P-TAU在AD疗法的临床试验中的作用，并构成对这种有希望的动物模型系统中其他潜在CSF生物标志物和其他潜在治疗疗法的未来研究的基础。 相关性：该项目有可能帮助开发更有效的方法来识别有前途的AD药物，从而导致临床试验需要更少的时间和金钱来完成。鉴于美国和其他工业化国家的迅速增长的老年人口中这种疾病的患病率的升高，促进更有效的AD的开发对NIA至关重要。