Using Genetic and Blood Metabolites to Understand the Risk of Alzheimer's Disease in Latinos

美国拉美裔美国人非常多样化，他们来自中美洲和南美洲，以及 加勒比海。与美国白人相比，拉美裔在社会经济上处于不利地位，并遭受着更高的 阿尔茨海默病和相关痴呆症的患病率。阿尔茨海默病的遗传决定因素可能是 拉美裔与白人略有不同：在初步结果中，我们发现遗传背景， 以从美洲印第安人(印第安人)祖先那里继承的基因组比例的形式减轻了 载脂蛋白E-𝜖𝜖4变异对西班牙裔社区个体认知功能下降的不利影响 健康研究/拉丁裔研究(HCHS/SOL)。这表明基于基因的机制具有异质性。 拉丁裔潜在的神经认知能力下降。 非靶向代谢组学是开发潜在的人类疾病生物标志物的一种很有前途的方法。上一首 代谢组学研究确定了阿尔茨海默病和认知特征的潜在生物标记物。 然而，以分段的方式，很少有专门针对拉丁裔的工作，而且遗传学和代谢组学 除了使用APOE-𝜖𝜖4之外，还没有集成用于风险预测。在这里，我们建议使用一个数据集 包括来自HCHS/SOL的约1500名年长的拉丁裔成年人，他们的代谢组学未达到基线水平 在基线和随访中对神经认知功能进行评估。我们的目标是：(1)发展 与衰老相关的认知衰退表型的初步生物标志物(例如，全局认知功能的变化， 轻度认知障碍)；(2)研究代谢物与认知衰退相关的遗传基础， 并根据遗传背景研究潜在的异质性；以及(3)形成建议和赠款 应用程序支持利用遗传学和代谢组学的更大规模的研究计划，以及潜在的其他 ‘组学，在不同的人群中开发阿尔茨海默病的生物标记物，并研究潜在的机制。

U.S. Latinos are highly diverse, with individuals originating from central and south America, as well as the Caribbean. Latinos are socioeconomically disadvantaged compared to U.S. Whites, and suffer from a higher prevalence of Alzheimer’s disease and related dementia. Genetic determinants of Alzheimer’s disease may be somewhat different in Latinos compared to Whites: in preliminary results, we found that genetic background, in the form of proportion of genome inherited from Amerindian (Native American) ancestors mitigates the detrimental effect of the APOE-𝜖𝜖4 variants on cognitive decline in individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). This suggests heterogeneity in genetically-based mechanisms underlying neurocognitive decline in Latinos. Untargeted metabolomics is a promising approach to develop potential biomarkers for human disease. Previous metabolomics studies identified potential biomarkers for Alzheimer’s disease and for cognitive traits in a cross- sectional manner, however, very little work was done specifically in Latinos, and the genetics and metabolomics have not been integrated for risk prediction, apart from using APOE-𝜖𝜖4. Here, we propose to utilize a dataset including ~1,500 older Latino adults from the HCHS/SOL with untargeted metabolomics measured at a baseline visit, and neurocognitive function estimated in both the baseline and a follow-up visit. Our goals are: (1) develop preliminary biomarkers for aging-related cognitive decline phenotypes (e.g. change in global cognitive function, mild cognitive impairment); (2) study the genetic basis of the association of metabolites with cognitive decline, and study potential heterogeneity by genetic background; and (3) form recommendations and a grant application to support a larger research program utilizing genetics and metabolomics, and potentially other ‘omics, to develop biomarkers of Alzheimer’s disease in diverse populations, and study underlying mechanisms.