Oral Glucose Tolerance Test for Alzheimer's Disease Biomarker Development

用于阿尔茨海默病生物标志物开发的口服葡萄糖耐量测试

• 批准号: 8089269
• 负责人: SUZANNE CRAFT
• 金额: $ 19.11万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-15 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8089269
• 关键词: Age; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Animal Model; Area Under Curve; Biological; Biological Markers; Blood; Blood specimen; Brain imaging; Clinical; Clinical Trials; Cognition; Cognitive; Control Groups; Cross-Sectional Studies; Data; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Early identification; Early treatment; Enzyme-Linked Immunosorbent Assay; Fasting; Future; Glucagon; Glucose; Human; Incidence; Individual; Kinetics; Longitudinal Studies; Measurement; Measures; Memory; Methods; Monitor; OGTT; Oral; Oral Administration; Participant; Pathologic; Patients; Peptides; Performance; Plasma; Process; Proteins; Recruitment Activity; Regulation; Reporting; Research; Research Personnel; Role; Sampling; Senile Plaques; Severity of illness; Solutions; Specific qualifier value; Staging; Testing; Therapeutic; Time; Universities; Washington; base; design; glucagon-like peptide; improved; incretin hormone; mild neurocognitive impairment; public health relevance; response; sex; tool

DESCRIPTION (provided by applicant): The studies in this application propose to develop a simple oral glucose tolerance test (OGTT) as a tool to enhance the utility of plasma amyloid-beta (A¿) as a biomarker of Alzheimer's disease (AD). Currently, there are many on-going clinical trials for potential treatment of AD. Therefore, it is important to be able to identify AD patients in the earlier stages who would be ideal candidates for these therapies. Plasma A¿ would be an inexpensive and non-invasive tool in diagnosing various stages of AD, as well as for monitoring A¿ modifying therapies. However, most cross-sectional studies involving plasma A¿ have not been able to show differences between individuals with AD compared to controls. In our project, we propose to "unmask" the differences between individuals who have normal cognition, mild cognitive impairment (MCI), and early AD (AD) by modulating the plasma A¿ levels with OGTT. We also propose to demonstrate that this effect may be due to lower glucagon-like peptide-1 (GLP-1) release in response to OGTT. In a cross-sectional study, we will administer OGTT to a group of individuals in each of the amnestic MCI (aMCI), AD and cognitively normal control groups. Plasma samples will be obtained at various time points and quantified for A¿ 42 and GLP-1 by ELISA. Then, we will compare at a single time point, the area under curve (AUC) of A¿ 42 kinetics in response to OGTT across the three groups, and also correlate it to the performance on tests of memory. We will also compare the AUC of plasma GLP-1 kinetics in response to OGTT, and correlate to the AUC of plasma A¿ 42 kinetics. The results of this exploratory study will provide data regarding the potential utility of OGTT modulated plasma A¿ 42 as a diagnostic biomarker of MCI and AD, as well as a biomarker of disease severity. It will also provide data on the potential relationship between GLP-1 to plasma A¿ 42 levels in response to OGTT. In addition, the data from this exploratory study will enable us to gather sufficient data to design a longitudinal study to demonstrate the utility of OGTT in differentiating subjects, monitor therapeutic response and predict disease progression. PUBLIC HEALTH RELEVANCE: The studies in this application propose to develop a simple oral glucose tolerance test as a tool to meaningfully assess plasma amyloid levels. As the incidence of Alzheimer's disease (AD) climbs and the biological and cognitive ramifications of such a disorder become more debilitating, the importance of early intervention is tremendous. Development of a reliable biomarker that is simple and non-invasive would enable early identification of individuals who are at risk for AD, and may allow earlier treatment.

描述（由申请人提供）：本申请中的研究提出开发一种简单的口服葡萄糖耐量试验（OGTT）作为工具，以增强血浆淀粉样蛋白β（A β）作为阿尔茨海默病（AD）生物标志物的效用。目前，有许多正在进行的潜在治疗AD的临床试验。因此，重要的是能够在早期阶段识别AD患者，这些患者将是这些治疗的理想候选人。血浆A将是一种廉价和非侵入性的工具，用于诊断AD的各个阶段，以及监测A修饰疗法。然而，大多数涉及血浆A？的横断面研究未能显示AD患者与对照组之间的差异。在我们的项目中，我们建议通过OGTT调节血浆A？水平来“揭示”具有正常认知、轻度认知障碍（MCI）和早期AD（AD）的个体之间的差异。我们还建议证明，这种效果可能是由于较低的胰高血糖素样肽-1（GLP-1）释放响应OGTT。 在一项横断面研究中，我们将对遗忘型MCI（aMCI）、AD和认知正常对照组中的一组个体进行OGTT。将在不同时间点采集血浆样本，并通过ELISA定量测定A 42和GLP-1。然后，我们将在单个时间点比较三组中响应于OGTT的A42动力学的曲线下面积（AUC），并且还将其与记忆测试的表现相关联。我们还将比较响应OGTT的血浆GLP-1动力学的AUC，并与血浆A 42动力学的AUC相关。 这项探索性研究的结果将提供关于OGTT调节的血浆A 42作为MCI和AD的诊断生物标志物以及疾病严重程度的生物标志物的潜在效用的数据。它还将提供GLP-1与OGTT后血浆A42水平之间潜在关系的数据。此外，来自该探索性研究的数据将使我们能够收集足够的数据来设计纵向研究，以证明OGTT在区分受试者、监测治疗反应和预测疾病进展方面的效用。 公共卫生关系：本申请中的研究提出开发一种简单的口服葡萄糖耐量试验作为有意义地评估血浆淀粉样蛋白水平的工具。随着阿尔茨海默病（AD）的发病率攀升，这种疾病的生物和认知后果变得更加衰弱，早期干预的重要性是巨大的。开发一种简单且非侵入性的可靠生物标志物将能够早期识别有AD风险的个体，并可能允许早期治疗。