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

目前，几乎所有关于阿尔茨海默病(AD)的分子生物标记物研究和临床试验都是 主要限于高加索人参与者。根本的问题是，按照目前的定义，AD是否是 非洲裔美国人，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， 处于临床前和症状阶段。到目前为止，相互矛盾的结果出现在关于 这个问题，很大程度上是由于已发表的研究中非裔美国人的样本量有限。我们建议 通过实施多中心、纵向、集中和标准化的研究来解决这些问题 对所有现有的和预期采集的脑脊液(CSF)样品进行再加工，磁性 磁共振成像(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。我们将与五个人联手 AD的主要生物标志物研究：华盛顿大学奈特阿尔茨海默病研究中心(ADRC)， 宾夕法尼亚大学AD核心中心，埃默里大学ADRC，哈佛大学老龄化大脑研究，以及 无症状阿尔茨海默病试验中的淀粉样蛋白治疗。我们将汇集可能是最大的生物标志物数据集 非洲裔美国人，并全面分析由此产生的AD生物标志物和认知数据 检查临床前阶段和症状阶段的种族差异。我们将进一步评估这些角色 AD的危险因素、载脂蛋白Eε4状态、家族史、年龄、性别、教育程度、社会经济地位和血管 负担在非裔美国人和高加索人之间的横截面和纵向差异中发挥作用。我们会 还确定了AD生物标志物对并发和纵向的可预测性的种族差异 认知结果。这些种族差异，如果被拟议的关于非洲最大的 美国生物标记物队列，可能意味着种族之间潜在的不同治疗反应，以及 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的试验。

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.