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: 10709216
• 负责人: Michelle M Mielke
• 金额: $ 43.46万
• 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/10709216
• 关键词: Acceleration; Accounting; African American; African American population; Age; Aging; Alzheimer' s Disease; Alzheimer’s disease biomarker; Amyloid; Biological; Biological Assay; Biological Markers; Biological Models; Blood specimen; COVID-19; Chronic Disease; Clinic; Clinical; Contracts; Data; Dementia; Development; Discrimination; Economics; Education; Family; Family and Community Health Study; Freezing; Genetic; Growth; Health; Illness impact; Income; Individual; Investigation; Life Style; Longitudinal Studies; Low income; Mediating; Nature; Nerve Degeneration; Observational Study; Pathologic Processes; Pathology; Pathway interactions; Persons; Physiological; Research; Research Personnel; Sampling; Sampling Studies; Stress; Testing; Time; Universities; Weather; blood-based biomarker; interest; parent grant; psychosocial wellbeing; social; stressor; tau-1

Project Summary (From Parent Grant AG077386) 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.

项目摘要 （来自父母赠款AG077386） 全球，超过5000万人患有痴呆症，阿尔茨海默氏病（AD）占70％ 在所有情况下。最近，NIA与阿尔茨海默氏症协会一起提出了一个生物定义 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志物可用于观察 研究并可能很快可用于临床利用。不幸的是，非洲裔美国人很少 包括在AT（N）框架的AD研究或研究中。鉴于他们是 至少是白人开发AD的可能性的两倍，证据表明该病理的本质（混合 与纯AD相比，与白人相比，非裔美国人的发作途径可能完全不同。 拟议的研究将使用家庭和社区健康研究（FACHS），这是一个独特的25年持续 研究数百个非洲裔美国家庭的身体和社会心理健康的研究，以调查 各种社会和经济压力源，生活方式和遗传因素，衰老率以及 慢性疾病会影响AT（N）生物标志物的轨迹。少数现有的非裔美国痴呆症研究使用 收入和教育更高的样本比普通非裔美国人人口。相比之下，Fachs 样本包含面临经济困难挑战的个人中很大一部分 低等教育和一生的歧视。我们的佐治亚大学调查员团队 蛋黄酱诊所将首先使用抽水的冷冻血液样本进行AT（N）生物标志物的测定 2008年和2019年以及2024年将获得的新一轮血液样本。这些数据将使我们能够 使用具有单独变化的时间点（年龄）的生长曲线来估计（n）的发育轨迹 生物标志物。接下来，我们将研究各种环境，生活方式的独特贡献 在（N）轨迹加速这些方面的生物学/生理因素。我们对测试特别感兴趣 健康的生物/生理标志物用于调解或调节生活方式和效果的模型 关于AT（N）生物标志物变化的环境环境。最后，目前正在收集COVID-19数据 从研究样本中，可以在拟议的项目中使用。因此，我们将能够检查 在（波5和8时）在（n）生物标志物增加了covid-19的机会，以及 疾病严重的病例在第9波第9波的标记处升高。

项目成果

Direct and Indirect Effects of Socioeconomic Status and Discrimination on Subjective Cognitive Decline: A Longitudinal Study of African American Women.

社会经济地位和歧视对主观认知下降的直接和间接影响：非裔美国妇女的纵向研究。

• DOI: 10.1093/geronb/gbad029
• 发表时间: 2023
• 期刊: The journals of gerontology. Series B, Psychological sciences and social sciences
• 作者: Simons,RonaldL;Ong,MeiLing;Beach,StevenRH;Lei,Man-Kit;Philibert,Robert;Mielke,MichelleM
• 通讯作者: Mielke,MichelleM

Correction to: Direct and Indirect Effects of Socioeconomic Status and Discrimination on Subjective Cognitive Decline: A Longitudinal Study of African American Women.

更正：社会经济地位和歧视对主观认知下降的直接和间接影响：非裔美国妇女的纵向研究。

• DOI: 10.1093/geronb/gbad073
• 发表时间: 2023
• 期刊: The journals of gerontology. Series B, Psychological sciences and social sciences