Cross Sectional and Longitudinal Racial Disparity in Molecular Biomarkers of Alzheimer Disease

阿尔茨海默病分子生物标志物的横向和纵向种族差异

• 批准号: 10604365
• 负责人: CHENGJIE XIONG
• 金额: $ 287.48万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10604365
• 关键词: African American population; Age; Alzheimer' s Disease; Alzheimer' s Disease Core Center; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Apolipoprotein E; Area; Biological Markers; Blood Vessels; Body mass index; Caucasians; Cerebrospinal Fluid; Clinical; Clinical Trials; Cognition; Cognitive; Data; Data Set; Databases; Dementia; Disease; Education; Family; Family history of; Future; Genotype; Glycosylated hemoglobin A; Goals; Hippocampus; Image; Lead; Literature; Longitudinal Studies; Magnetic Resonance Imaging; Modality; Multicenter Studies; Nature; Outcome; Participant; Pennsylvania; Persons; Phosphorylation; Play; Population Heterogeneity; Positron-Emission Tomography; Prevention trial; Protocols documentation; Publishing; Race; Recording of previous events; Research; Risk Factors; Role; Sample Size; Sampling; Scanning; Socioeconomic Status; Standardization; Statistical Models; Tracer; Underrepresented Populations; Universities; Washington; White Matter Hyperintensity; Work; aging brain; asymptomatic Alzheimer' s disease; cognitive change; cohort; deprivation; design; efficacious treatment; healthy aging; indexing; mild cognitive impairment; molecular marker; pre-clinical; prospective; racial difference; racial disparity; rate of change; sex; structural imaging; tau Proteins; treatment response; treatment trial; uptake

Currently, almost all molecular biomarker studies in Alzheimer disease (AD) and clinical trials on AD have been largely limited to Caucasian participants. The fundamental question is whether AD, as currently defined, is the same disease for African Americans, the largest under-represented group (URG) in the US, and Caucasians, both in the preclinical and symptomatic stages. Conflicting results have thus far appeared in the literature about this very question, largely due to the limited sample sizes of African Americans in published studies. We propose to tackle these problems by implementing a multi-center and longitudinal study with a central and standardized re-processing of all currently existing and prospectively collected cerebrospinal fluid (CSF) samples, magnetic resonance imaging (MRI) structural scans, and positron emission tomography (PET) beta-amyloid and PET tau imaging scans, in addition to a harmonization of clinical and cognitive outcomes. We will join forces with five major biomarker studies of AD: the Washington University Knight Alzheimer Disease Research Center (ADRC), University of Pennsylvania AD Core Center, Emory University ADRC, Harvard Aging Brain Study, and the Anti- Amyloid Treatment in Asymptomatic Alzheimer's trial. We will assemble likely the largest biomarker data set of African Americans, and analyze resulting AD biomarker and cognitive data in a comprehensive manner to examine the racial disparity in both the preclinical and the symptomatic stages. We will further assess the roles that AD risk factors, APOE ε4 status, family history, age, sex, education, socioeconomic status, and vascular burden play in cross sectional and longitudinal differences between African Americans and Caucasians. We will also determine the racial differences in the predictability of AD biomarkers to concurrent and longitudinal cognitive outcomes. These racial differences, if confirmed by the proposed study on the largest African Americans biomarker cohort, may imply potentially differential treatment responses between the races, and hence will have profound implications to the design and analyses of ongoing and future prevention and treatment trials of AD.

目前，几乎所有阿尔茨海默病（AD）的分子生物标志物研究和AD的临床试验都已完成。 主要限于高加索参与者。最根本的问题是，按照目前的定义，AD是否是 非裔美国人（美国最大的代表性不足群体（URG））和高加索人也患有同样的疾病， 无论是在临床前阶段还是症状阶段。到目前为止，文献中已经出现了关于 这个问题，很大程度上是由于在已发表的研究中，非洲裔美国人的样本量有限。我们提出 通过实施多中心和纵向研究来解决这些问题， 对所有现有和前瞻性采集的脑脊液（CSF）样本进行再处理，磁性 共振成像（MRI）结构扫描，以及正电子发射断层扫描（PET）β-淀粉样蛋白和PET tau 成像扫描，以及临床和认知结果的协调。我们将联合五个 AD的主要生物标志物研究：华盛顿大学KnightAlzheimer病研究中心（ADRC）， 宾夕法尼亚大学AD核心中心、埃默里大学ADRC、哈佛衰老大脑研究和抗衰老大脑研究。 淀粉样蛋白治疗无症状阿尔茨海默氏症试验。我们将收集可能是最大的生物标志物数据集， 非裔美国人，并以全面的方式分析所得的AD生物标志物和认知数据， 检查在临床前和症状阶段的种族差异。我们将进一步评估 AD危险因素、APOE ε4状态、家族史、年龄、性别、教育、社会经济地位和血管 非裔美国人和高加索人之间的横向和纵向差异的负担。我们将 还确定了AD生物标志物对同时和纵向的可预测性的种族差异。 认知结果。这些种族差异，如果得到拟议中的对非洲最大的 美国人生物标志物队列可能意味着种族之间可能存在差异的治疗反应，并且 因此将对正在进行的和未来的预防和治疗的设计和分析产生深远的影响 AD的审判