Stress, Weathering, and Blood-Based Biomarkers of Alzheimer’s Disease: A Longitudinal Study of Low Income, Aging African Americans

项目摘要 在世界范围内，超过5000万人患有痴呆症，其中阿尔茨海默病(AD)占70% 在所有案件中。最近，NIA与阿尔茨海默氏症协会联合提出了一个生物学定义 基于淀粉样蛋白(A)、磷酸化tau(T)和 神经变性(N)。值得注意的是，AT(N)的基于血液的生物标记物现在可用于观察 正在研究，可能很快就会投入临床使用。不幸的是，非洲裔美国人很少 包括在AD研究或AT(N)框架的调查中。这种省略是至关重要的，因为它们是 患阿尔茨海默病的可能性至少是白人的两倍，有证据表明，这种病理的性质(混合 与纯AD相比)，与白人相比，非裔美国人的发病途径可能有很大不同。 拟议的研究将使用家庭和社区健康研究(FACHS)，这是一项为期25年的独特研究 对数百个非裔美国家庭的身体和心理社会幸福感的研究，以调查 各种社会和经济压力、生活方式和遗传因素、老龄化速度和 慢性疾病对AT(N)生物标志物的影响少数现存的非裔美国人痴呆症研究使用 收入和受教育程度高于一般非裔美国人的样本。相比之下，FACHS 样本中包含了面临经济困难挑战的相当大比例的个人， 受教育程度低，而且一生中大部分时间都受到歧视。我们来自佐治亚大学的调查组 梅奥诊所将开始使用冰冻血液样本进行AT(N)生物标记物的分析 2008年和2019年，以及将于2024年获得的新一轮血液样本。这些数据将使我们能够 用不同时间点(年龄)的生长曲线估计AT(N)的发育轨迹 生物标志物。接下来，我们将调查各种环境、生活方式和 加速这些AT(N)轨迹的生物/生理因素。我们对测试特别感兴趣 健康的生物/生理标记物起到调节或调节生活方式和 环境环境对AT(N)生物标志物变化的影响最后，目前正在收集新冠肺炎的数据 来自研究样本，并将在拟议项目中使用。因此，我们将能够检查 第五波和第八波的AT(N)生物标记物是否会增加感染新冠肺炎的机会，以及如果 病情严重者第9波AT(N)标志物升高。

Project Summary Worldwide, over 50 million people have dementia, with Alzheimer's disease (AD) accounting for as much as 70% of all cases. Recently, the NIA in conjunction with the Alzheimer's Association has proposed a biological definition of AD based on the underlying pathological processes of amyloid (A), phosphorylated tau (T), and neurodegeneration (N). Notably, blood-based biomarkers of AT(N) are now available for use in observational studies and may soon be available for clinical utilization. Unfortunately, African Americans have rarely been included in studies of AD or investigations of the AT(N) framework. This omission is critical given that they are at least twice as likely as whites to develop AD and evidence suggests that the nature of the pathology (mixed versus pure AD) and the pathways to onset may be quite different for African Americans compared to whites. The proposed research will use use the Family and Community Health Study (FACHS), a unique 25-year ongoing study of physical and psychosocial well-being among several hundred African American families, to investigate the extent to which a variety of social and economic stressors, lifestyle and genetic factors, rate of aging, and chronic illness impact trajectories of AT(N) biomarkers. The few extant African American dementia studies use samples with higher income and education than the general African American population. In contrast, the FACHS sample contains a substantial proportion of individuals who have faced the challenges of economic hardship, low education, and discrimination for most of their lives. Our team of investigators from the University of Georgia and the Mayo Clinic will begin by performing assays of AT(N) biomarkers using frozen blood samples drawn in 2008 and 2019, as well as a new round of blood samples to be obtained in 2024. These data will enable us to use growth curves with individually varying time points (age) to estimate developmental trajectories of AT(N) biomarkers. Next, we will investigate the unique contributions of various environmental, lifestyle, and biological/physiological factors in accelerating these AT(N) trajectories. We are especially interested in testing models where biological/physiological markers of health serve to mediate or moderate the effect of lifestyle and environmental circumstances on changes in AT(N) biomarkers. Finally, Covid-19 data is currently being collected from the study sample and will be available for use in the proposed project. Thus, we will be able to examine whether AT(N) biomarkers at waves 5 and 8 increase the chances of contracting Covid-19, as well as if having suffered a severe case of the illness elevates AT(N) markers at wave 9.