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

阿尔茨海默病(AD)对拉美裔美国人--美国增长最快的老年人群体--的影响比例高于高加索人，而且年龄更小。这些差异的原因尚不清楚，部分原因是西班牙裔在AD研究中的代表性不足。揭示这种差异的原因可能会提供对AD原因的洞察，并有助于开发解决方案，这也是本项目的目标。强有力的研究发现将社区的社会和身体特征与认知健康联系在一起，而社区-埃尔·巴里奥-已知对西班牙裔人口很重要。然而，确定影响AD风险的特定背景和个人因素是一个复杂的问题。该项目旨在通过一种新的方法来确定邻居因素对拉美裔美国人类AD认知轨迹的影响，该方法结合了1)高维多组学(遗传和代谢分子标记)揭示的个体差异和2)家庭和邻居动态的调节/调节。我们接触到墨西哥裔美国人队列--圣安东尼奥墨西哥裔美国人家庭研究(SAFS)--将使我们能够测试，不同社区之间类似AD的认知轨迹的差异是完全由个人特征解释的，还是至少部分取决于社区的社会和身体因素。近30年来，SAFS参与者的特征一直很深刻，包括临床(心脏代谢和认知轨迹)、结构性神经成像和环境数据；全基因组测序(WGS)和其他组学(例如代谢谱、表观基因组学、蛋白质和RNA表达模式)。这个项目的具体目标是：1)确定在墨西哥裔美国人中，与非AD样认知衰退相比，家族主义是否提供了对AD样认知衰退的保护；2)通过对17个社区的在线街道图像分析，分析不同社区的社会和建成环境与AD样认知轨迹之间的关联，每个社区内至少有30名SAFS参与者；3)检测社区和家庭层面的环境(社会和空间)信号，反映在我们发现的与AD样认知衰退风险相关的任何高维代谢/脂肪组、表观基因组和转录生物标记物中；以及4)利用研究结果为社区项目提供指导，旨在通过开发战略沟通工具包和召开一个论坛，让不同的利益相关者参与进来，特别是社区设计师和城市规划师，从而降低类似AD的认知衰退的风险。总体而言，这些结果将阐明邻居特有的因素导致拉美裔人AD样认知下降的途径，为缓解AD提供新的方法。

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.