Clinical Core

临床核心

• 批准号: 10663867
• 负责人: DAVID A WOLK
• 金额: $ 73.86万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10663867
• 关键词: Achievement; African American population; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Attention; Autopsy; Awareness; Biological; Biological Markers; Brain; Caring; Cerebrospinal Fluid; Cerebrovascular Disorders; Cerebrum; Classification; Classification Scheme; Clinical; Clinical Data; Clinical Research; Clinical Trials; Cognition; Cognitive; Collaborations; DNA; Data; Data Set; Dementia; Disease; Doctor of Philosophy; Early Onset Alzheimer Disease; Economic Factors; Elderly; Epigenetic Process; Frontotemporal Dementia; Frontotemporal Lobar Degenerations; Genetic; Genetic Materials; Genomics; Goals; Heterogeneity; Image; Individual; Institution; International; Intervention Studies; Lewy Body Disease; Light; Link; Magnetic Resonance Imaging; Measures; Mechanics; Mission; National Institute on Alcohol Abuse and Alcoholism; Nerve Degeneration; Neurofibrillary Tangles; Onset of illness; Participant; Pathologic; Pathologist; Pathology; Persons; Phenotype; Plasma; Positron-Emission Tomography; Process; Research; Research Personnel; Risk; Role; Sampling; Senile Plaques; Site; Source; System; Training; Validation; White Matter Hyperintensity; base; biomarker development; brain tissue; cardiovascular risk factor; clinical diagnosis; clinical phenotype; cognitive reserve; cohort; comorbidity; data integration; data management; disease heterogeneity; disorder risk; diverse data; education research; ethnoracial; imaging program; in vivo; molecular marker; neuroimaging; neuropathology; next generation; normal aging; outreach; pre-clinical; protein TDP-43; recruit; research study; resilience; social factors; social health determinants; sociodemographic factors; synuclein; tau Proteins

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.

临床核心项目总结 宾夕法尼亚州ADRC的主题是更好地了解上游因素和过程， 阿尔茨海默病（AD）异质性和下游标志物的关键特征。 临床核心作为这一主题使命的中心节点，通过深入描述临床和 人口统计学差异队列（目标1）。考虑到理解异质性在 整个AD连续体，我们将招募，评估，并纵向跟踪一个队列，ADRC UDS队列， 从认知正常的老年人到轻度痴呆症患者。为了捕捉表型多样性和重叠 与其他神经退行性疾病，队列包括额颞叶痴呆（FTD），路易体 疾病，以及非典型和早发性AD表现。与外联、征聘和 参与核心（ORE），招募非裔美国人，一个在AD研究中代表性很低的群体， 这也是一个优先事项，并加强努力，审查造成异质性的各种因素， 疾病的表达（目的3）。 在AD从被定义为临床诊断转变为由以下定义的疾病的背景下， 生物标志物，宾夕法尼亚州ADRC拥抱生物标志物的采集和验证的重要性。临床 Core通过采集血浆、脑脊液以及MRI和PET成像来促进这些工作 (Aim 2）。这些材料和数据是与生物标志物和神经影像学密切合作获得的。 核心和允许分类的基础上存在或不存在脑b-淀粉样蛋白的个人 斑块（A）、基于tau的神经元缠结（T）和神经变性（N）。因此，在尽可能多的参与者中， 如果可能，我们将获得生物流体（CSF和血浆）和/或神经影像学A/T/（N）指定。捕捉 脑血管疾病（CVD）在AD异质性中的作用，我们将获得临床、生物流体和神经影像学资料， CVD的风险或下游表现的测量（例如，白色高信号）。临床核心 也将是与基因组学一起获得的遗传物质和脑组织的来源， 神经病理学核心，将与上述生物标志物和临床数据相关联。 鉴于对疾病风险、表型和恢复力与脆弱性的潜在调节作用，我们 还将获得健康的社会决定因素的措施（SDoH;目标4），这可能会提供一个 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病研究所分享这一丰富多样的数据集和材料外， 协调中心（NACC）和其他ADRC和机构，临床核心参与了许多 多地点协作临床研究和干预研究，目标是促进对患有 AD/ADRD（目标5）。最后，临床核心作为研究培训工作的重要基础 教育部分，以培养下一代的研究者和临床医生。