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

压力、风化和阿尔茨海默病的血液生物标志物：对低收入、老龄化非裔美国人的纵向研究

• 批准号: 10441978
• 负责人: Michelle M Mielke
• 金额: $ 278.88万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10441978
• 关键词: Acceleration; Accounting; African American; African American population; Age; Aging; Alcohol consumption; Alzheimer' s Disease; Alzheimer' s Disease Pathway; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Amyloidosis; Biological; Biological Aging; Biological Assay; Biological Markers; Biological Models; Blood; Blood Glucose; Blood specimen; Body mass index; C-reactive protein; COVID-19; Cardiovascular Diseases; Caucasians; Chronic; Chronic Disease; Chronic stress; Clinic; Clinical; Contracts; Data; Dementia; Development; Diabetes Mellitus; Diet; Discrimination; Disease; Economics; Education; Epigenetic Process; Etiology; Exercise; Exposure to; Family; Family and Community Health Study; Fostering; Freezing; Generations; Genetic; Genetic Risk; Glial Fibrillary Acidic Protein; Glycosylated hemoglobin A; Growth; Health; Illness impact; Income; Individual; Inflammation; Intercept; Investigation; Kidney Diseases; Life Style; Light; Longitudinal Studies; Low income; Measures; Mediating; Modeling; National Institute on Aging; Nature; Nerve Degeneration; Not Hispanic or Latino; Observational Study; Participant; Pathologic Processes; Pathology; Pathway interactions; Patient Self-Report; Pattern; Persons; Physiological; Play; Population; Poverty; Religion; Research; Research Personnel; Risk Factors; Role; Sampling; Sampling Studies; Sex Differences; Smoking; Social support; Stress; Testing; Time; United States National Institutes of Health; Universities; Weather; base; blood-based biomarker; childhood adversity; cytokine; hazard; inflammatory marker; interest; lifestyle factors; methylomics; neighborhood disadvantage; neurofilament; polygenic risk score; predictive marker; psychosocial; psychosocial wellbeing; racial discrimination; resilience; sex; social; stressor; symposium; tau Proteins; tau-1; vector

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.

项目概要 全球有超过 5000 万人患有痴呆症，其中阿尔茨海默病 (AD) 占比高达 70% 所有案例中。最近，NIA联合阿尔茨海默病协会提出了一个生物学定义 AD 的诊断基于淀粉样蛋白 (A)、磷酸化 tau (T) 和 神经变性（N）。值得注意的是，基于血液的 AT(N) 生物标志物现在可用于观察 研究并可能很快用于临床应用。不幸的是，非裔美国人很少 包含在 AD 研究或 AT(N) 框架调查中。鉴于它们是 患 AD 的可能性至少是白人的两倍，并且有证据表明，这种病理学的本质（混合） 与纯 AD 相比），并且与白人相比，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)，这是一项持续 25 年的独特研究 对数百个非裔美国家庭的身心健康状况进行研究，以调查 各种社会和经济压力、生活方式和遗传因素、衰老速度和 慢性疾病影响 AT(N) 生物标志物的轨迹。现存的少数非裔美国人痴呆症研究使用 收入和教育程度高于一般非裔美国人的样本。相比之下，FACHS 样本中包含很大一部分面临经济困难挑战的个人， 他们受教育程度低，一生中大部分时间都受到歧视。我们来自佐治亚大学的研究团队 梅奥诊所将首先使用抽取的冷冻血液样本对 AT(N) 生物标志物进行检测。 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 使用具有个体不同时间点（年龄）的生长曲线来估计 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/生理标志物可以调节或调节生活方式和生活方式的影响的模型 环境条件对 AT(N) 生物标志物变化的影响。最后，目前正在收集 Covid-19 数据 来自研究样本，并将可用于拟议的项目。因此，我们将能够检查 第 5 波和第 8 波的 AT(N) 生物标志物是否会增加感染 Covid-19 的机会，以及是否有 患有严重疾病的患者会在第 9 波时升高 AT(N) 标记。