Multi-omic Investigation of Exercise Effects in Mild Cognitive Impairment

阿尔茨海默病（Alzheimer's disease，AD）是最常见的年龄相关性痴呆，正迅速成为一种主要的公共疾病 健康问题。目前，AD还没有治愈或改善疾病的疗法。没有治愈的选择 或甚至延迟AD的发作，经济成本、医疗负担和对受折磨个体的影响， 家庭和社会将是毁灭性的。本项目的总体目标是检验有氧运动的效果 使用代谢组学和蛋白质组学标记对中枢代谢途径进行锻炼。我们会用鲜血 来自350名MCI老年人的样本参加了由ADCS资助的EXERT研究。本研究 两个主要的结果指标将是24种代谢物和21种蛋白质的定量水平， 出版的panel主要的独立措施将是运动条件（有氧运动，伸展， 在EXERT研究中。对于主要分析，这将是一项重复测量， 受试者设计检查运动组对代谢组学和蛋白质组学测量的影响。中 模型开发臂，我们将整合代谢组学和蛋白质组学的措施， 更具体的多组学模型，可能比已经建立的模型对运动效应更敏感 单独的面板。使用多组学和个人面板，我们还将尝试预测运动对 个体参与者基线数据。我们将研究代谢组学、蛋白质组学和多- 其他EXERT结局的组学指标，包括淀粉样蛋白和tau蛋白的CSF指标， 成像和其他血液测量。最后，在探索性分析中， 代谢组学定量约4700种代谢物，以确定是否可以 鉴定我们的团队由经验丰富的基础和临床科学家，临床试验员， 生物统计学家的资源来执行这个项目。这项试验的结果将阐明代谢 运动作为治疗和可能预防阿尔茨海默病的机制。多组学面板 来自非靶向代谢组学的代谢组学小组可能为检测阿尔茨海默氏症提供新的途径 并在未来的临床试验中监测治疗效果。

Alzheimer's disease (AD) is the most common age-related dementia, and is rapidly becoming a major public health problem. At present, there are no cures or disease-modifying therapies for AD. Without options to cure or even delay the onset of AD, the economic costs, healthcare burden, and impact on afflicted individuals, their families, and society will be devastating. The overall goal of this project is to examine the effect of aerobic exercise on central metabolic pathways using metabolomic and proteomic markers. We will leverage blood samples from 350 older adults with MCI enrolled in the funded ADCS-funded EXERT study. In this study, the two primary outcome measures will be quantitative levels of 24 metabolites and 21 proteins from previously published panels. The main independent measure will be exercise condition (aerobic exercise, stretching, sedentary) in the EXERT study. For the primary analyses, this will be a repeated measures, within-and- between subjects design examining exercise group effects on the metabolomic and proteomic measures. In a model development arm, we will integrate the metabolomic and proteomic measures in a putatively richer and more specific multi-omic model which may be more sensitive to exercise effects than the already established individual panels. Using the multi-omic and individual panels, we will also attempt to predict exercise effects for individual participants from baseline data. We will examine change in the metabolomic, proteomic, and multi- omic measures for other EXERT outcomes including CSF measures of amyloid and tau, brain atrophy from imaging, and other blood measures. Finally, in an exploratory analysis, we will perform untargeted metabolomic quantification of ~4700 metabolites to determine if more specific metabolomic panels may be identified. Our team is comprised of experienced basic and clinical scientists, clinical trialists, and biostatisticians with the resources to carry out this project. The results of this trial will elucidate metabolic mechanisms of exercise as a treatment and possibly prevention of Alzheimer's disease. The multi-omic panel and metabolomic panel from the untargeted metabolomics may provide new avenues for detecting Alzheimer's disease and for monitoring treatment effects in future clinical trials.