Clinical Core

临床核心项目摘要 宾夕法尼亚大学亚洲发展研究中心的主题是更好地了解上游因素和有助于 与阿尔茨海默病(AD)的异质性以及对表征该疾病至关重要的下游标志物有关。这个 临床核心作为这一主题任务的中心节点，通过深入描述临床和 人口结构多样化的队列(目标1)。鉴于在以下背景下理解异构性的重要性 在整个AD连续体中，我们将招募、评估并纵向跟踪ADRC UDS队列，即 涵盖认知正常的老年人和轻度痴呆症患者。捕捉表型多样性和重叠 对于其他神经退行性疾病，队列包括额颞部痴呆(FTD)、路易体 疾病，以及不典型和早发性阿尔茨海默病。与外联、征聘和 参与核心(ORE)，招募非裔美国人，一个在AD研究中很少被代表的群体，是 也是一个优先事项，并加强努力，以审查造成异质性的各种因素 疾病表现(目标3)。 在AD从被定义为临床诊断到被定义为 对于生物标记物，宾夕法尼亚大学ADRC接受了生物标记物获取和验证的重要性。《临床》 Core通过获取血浆、脑脊液以及MRI和PET成像来促进这些工作 (目标2)。这些材料和数据是通过与Biomarker和神经成像密切合作获得的 核心，并允许根据大脑b-淀粉样蛋白的存在或不存在对个体进行分类 斑块(A)、基于tau的神经原纤维缠结(T)和神经变性(N)。因此，在尽可能多的参与者中 有可能，我们将获得生物液(脑脊液和血浆)和/或神经成像A/T/(N)称号。为了捕捉到 脑血管疾病(CVD)在AD异质性中的作用，我们将获得临床、生物液体和神经成像 测量心血管疾病的风险或下游表现(例如，脑白质高信号)。临床核心 也将是遗传物质和脑组织的来源，与基因组学和 神经病理学核心，将与上述生物标记物和临床数据联系起来。 鉴于疾病风险、表型和复原力与脆弱性之间的潜在调节作用，我们 还将获得健康的社会决定因素的衡量标准(SDoH；目标4)，这可能会提供 更深入地了解种族差异在疾病风险和表现中的作用。 除了与国家阿尔茨海默氏症协会分享这一丰富多样的数据集和材料外， 协调中心(NACC)以及其他ADRC和机构，临床核心参与了许多 多点协作临床研究和干预研究，目标是促进对患有糖尿病的患者的护理 AD/ADRD(目标5)。最后，临床核心是研究培训工作的重要基础 教育部分，以培养下一代研究人员和临床医生。

Clinical Core Project Summary The theme of the Penn ADRC is to better understand both the upstream factors and processes that contribute to Alzheimer’s Disease (AD) heterogeneity and the downstream markers critical to characterizing it. The Clinical Core serves as the central node for this thematic mission by deeply characterizing a clinically and demographically diverse cohort (Aim 1). Given the importance of understanding heterogeneity in the context of the entire AD continuum, we will recruit, assess, and longitudinally follow a cohort, the ADRC UDS Cohort, that spans cognitively normal older adults to those with mild dementia. To capture phenotypic diversity and overlap with other neurodegenerative conditions, the cohort includes frontotemporal dementia (FTD), Lewy Body disease, and atypical and early onset AD presentations. In collaboration with the Outreach, Recruitment, and Engagement Core (ORE), recruitment of African Americans, a group poorly represented in AD research, is also a priority and enhances efforts to examine the diversity of factors that contribute to heterogeneity in expression of disease (Aim 3). In the context of the transformation of AD from being defined as a clinical diagnosis to a disease defined by biomarkers, the Penn ADRC embraces the importance of biomarker acquisition and validation. The Clinical Core facilitates these efforts through acquisition of plasma, cerebrospinal fluid, and MRI and PET imaging (Aim 2). These materials and data are obtained in close collaboration with the Biomarker and Neuroimaging Cores and allow for classification of individuals on the basis of the presence or absence of cerebral b-amyloid plaques (A), tau-based neurofibrillary tangles (T), and neurodegeneration (N). Thus, in as many participants as possible, we will obtain biofluid (CSF and plasma) and/or neuroimaging A/T/(N) designation. To capture the role of cerebrovascular disease (CVD) in AD heterogeneity, we will obtain clinical, biofluid, and neuroimaging measures of risk or downstream manifestations of CVD (e.g. white matter hyperintensities). The Clinical Core will also be a source of genetic material and brain tissue obtained in conjunction with the Genomics and Neuropathology Cores, which will be linked to the above biomarker and clinical data. In light of the potential modulating effect on disease risk, phenotype, and resilience versus vulnerability, we will also obtain measures of social determinants of health (SDoH; Aim 4), which potentially will provide a deeper understanding of the role of ethnoracial differences in disease risk and presentation. In addition to the sharing of this rich and diverse dataset and materials with the National Alzheimer’s Coordinating Center (NACC) and with other ADRCs and institutions, the Clinical Core participates in numerous multi-site collaborative clinical research and intervention studies with the goal of advancing care of people with AD/ADRD (Aim 5). Finally, the Clinical Core serves as an important base for training efforts with the Research Education Component to develop the next generation of investigators and clinicians.