Integration of Socio-Spatial Data for Neighborhoods with Multi-omic profiles to Identify and Mitigate Factors Affecting Risk of ALzheimer's Disease

将社区的社会空间数据与多组学概况相整合，以识别和减轻影响阿尔茨海默病风险的因素

• 批准号: 10095572
• 负责人: Gladys E. Maestre
• 金额: $ 290.6万
• 依托单位: UNIVERSITY OF TEXAS RIO GRANDE VALLEY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10095572
• 关键词: Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Biological Markers; Caucasians; Characteristics; Cities; Clinical; Cognitive; Communication; Complex; Data; Elderly; Elements; Environment; Family; Family Study; Genetic; Genetic Transcription; Goals; Health; Hispanic Americans; Hispanics; Imagery; Impaired cognition; Individual; Individual Differences; Knowledge; Latino; Link; Mediation; Metabolic; Mexican Americans; Neighborhoods; Participant; Pathway interactions; Pattern; Population; Process; Research; Signal Transduction; Social Environment; Structure; Testing; Variant; base; built environment; cardiometabolism; cohort; epigenomics; genome sequencing; high dimensionality; improved outcome; insight; metabolic profile; metabolomics; molecular marker; multiple omics; neuroimaging; novel strategies; protein expression; social; transcriptomics; whole genome

Alzheimer’s disease (AD) affects a higher proportion of Hispanics - the fastest growing group of older adults in the U.S. - than Caucasians, and at younger ages. The causes of these differences are unknown, partly due to underrepresentation of Hispanics in AD research. Uncovering the reasons for this disparity may provide insight into the causes of AD and help to develop solutions and is this project's goal. Robust findings have linked the social and physical characteristics of neighborhoods to cognitive health, and the neighborhood - el barrio - is known to be important to Hispanic populations. However, identifying specific contextual and individual factors that affect risk of AD is a complex problem. This project aims to determine the effects of neighborhood factors on AD-like cognitive trajectories in Hispanic Americans, by a novel approach that integrates 1) individual differences revealed by high-dimensional multi-omics (genetic and metabolic molecular markers) and 2) mediation/moderation by family and neighborhood dynamics. Our access to a Mexican American cohort - the San Antonio Mexican American Family Study (SAFS) - will enable us to test if variations in AD-like cognitive trajectories across neighborhoods are explained exclusively by individual characteristics, or depend at least partly on social and physical elements of neighborhoods. SAFS participants have been deeply characterized for almost 30 years, including clinical (cardiometabolic and cognitive trajectories), structural neuroimaging, and environmental data; whole-genome sequencing (WGS), and other -omics (e.g., metabolic profiles, epigenomics, protein and RNA expression patterns). The specific aims of this project are to 1) determine if familism provides protection from AD-like cognitive decline compared to non-AD like cognitive decline in Mexican Americans; 2) analyze the associations between social and built environments of different neighborhoods and AD-like cognitive trajectories, by using online street imagery analysis of 17 neighborhoods within each of which at least 30 SAFS participants reside; 3) detect environmental (social and spatial) signals at neighborhood and family levels, reflected in any high-dimensional metabolomic/lipidomic, epigenomic, and transcriptomic biomarkers we find correlated with risk of AD-like cognitive decline; and 4) exploit the results to provide guidance for neighborhood-based projects aimed at decreasing the risk of AD-like cognitive decline, by developing a strategic communication toolkit, and convening a forum that will engage diverse stakeholders, particularly neighborhood designers and city planners. Overall, the results will elucidate pathways through which neighborhood-specific factors contribute to AD-like cognitive decline in Hispanics, offering new approaches to mitigation of AD.

阿尔茨海默氏病（AD）比高加索人和年轻时代更高的西班牙裔西班牙裔（美国成年人成年人成年人最快的老年人）影响。这些差异的原因是未知的，部分原因是AD研究中西班牙裔人的代表性不足。揭示这种差异的原因可能会洞悉广告的原因并帮助开发解决方案，这是该项目的目标。强大的发现将社区的社会和身体特征与认知健康联系起来，而邻里 - 埃尔·巴里奥（El Barrio）对西班牙裔人口很重要。但是，确定影响AD风险的特定上下文和个人因素是一个复杂的问题。该项目的目的是通过一种整合1）高维多词（遗传和代谢分子标记物）和2）家庭和邻里动力学的新方法来确定邻里邻里对西班牙裔美国人的类似AD样认知轨迹的影响。我们进入墨西哥裔美国人队列（圣安东尼奥墨西哥裔美国家庭研究（SAFS））将使我们能够测试是否仅通过个人特征来解释整个社区的广告样认知轨迹的变化，或者至少部分依赖社区的社会和身体元素。 SAFS参与者已经深入了近30年的深刻特征，包括临床（心脏代谢和认知轨迹），结构神经影像学和环境数据；全基因组测序（WGS）和其他 - 组（例如，代谢谱，表观基因组学，蛋白质和RNA表达模式）。该项目的具体目的是1）确定熟悉程度是否提供了与墨西哥裔美国人认知能力下降相比，熟悉度是否提供了防止类似广告的认知能力下降； 2）分析不同社区和类似广告的认知轨迹的社交环境和建筑环境之间的关联，通过对17个社区的在线街道图像分析，每个社区至少有30个SAFS参与者居住； 3）在任何高维代谢组/脂质组，表观遗传组和转录生物标志物中都反映在邻里和家庭水平上的环境（社会和空间）信号，我们发现与AD样认知能力下降的风险相关； 4）利用结果为基于邻里的项目提供指导，旨在通过开发战略性沟通工具包来降低类似广告的认知能力下降的风险，并召集一个论坛，该论坛将吸引潜水员利益相关者，尤其是邻里设计师和城市规划师。总体而言，结果将阐明途径通过哪些邻里特定因素导致西班牙裔类似广告的认知能力下降，从而提供缓解AD的新方法。