Core B: Clinical Core

核心 B：临床核心

• 批准号: 10264189
• 负责人: Richard J. Caselli
• 金额: $ 93.9万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-05 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10264189
• 关键词: Address; Age; Alleles; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer’s disease biomarker; Amyloid beta-Protein; Arizona; Autopsy; Biological; Biological Markers; Blood; Blood specimen; Brain; Brain imaging; Catchment Area; Clinical; Cognitive; Communities; DNA; Data; Data Set; Dementia; Development; Diagnosis; Dose; Early Diagnosis; Enrollment; Evaluation; Genetic Markers; Genetic Risk; Genotype; Goals; Grant; Heterozygote; Hispanics; Homozygote; Latino; Liquid substance; Magnetic Resonance Imaging; Measurement; Native Americans; Parkinson Disease; Participant; Plasma; Positron-Emission Tomography; Prevention therapy; Prevention trial; Research; Research Personnel; Resource Sharing; Resources; Risk; Sampling; Site; Standardization; Validation; Work; base; biomarker development; blood-based biomarker; clinical research site; cohort; data resource; data sharing; data sharing networks; design; drug development; high risk; interest; mild cognitive impairment; neuropathology; preclinical study; prevent; programs; recruit; resilience; resistance factors; tau Proteins

PROJECT SUMMARY/ABSTRACT – CLINICAL CORE The Clinical Core (CC) of the Arizona ADRC is a consortium of five recruitment sites providing catchment areas throughout Phoenix and Tucson that comprise a standardized unit under a single Clinical Core Director. The CC has an overarching interest in the study of preclinical Alzheimer's disease (AD) and the accelerated evaluation of AD prevention therapies with emphasis on the development of blood-based biomarkers (BBBs). The CC will provide NACC-shared uniform data sets (UDS) and brain images and NCRAD-shared CSF, DNA and blood samples from about 1,650 well characterized longitudinally assessed research participants in our ADRC grant- supported Clinical Core, our organizationally and philanthropically supported Affiliated Brain and Body Donation Program (BBDP) and Affiliated APOE Program, and our pending NIA grant-supported APOE4/APOE2 Allelic Dose Cohort. Our Clinical Core will include 550 annually assessed dementia, mild cognitive impairment (MCI) and cognitively unimpaired participants, including about 300 who are enrolled our BBDP, about 200 from Arizona's underrepresented Hispanic/Latino and Native American communities, and those originally cognitively unimpaired participants in our Affiliated APOE Program and APOE4/APOE2 Allelic Dose Cohort after they progress to MCI and dementia. Our Affiliated BBDP will include about 500 additional participants in our BBDP with and without the clinical manifestations of AD, Parkinson's disease, and related dementias (ADRD), providing a combined resource of data and samples from about 800 BBDP participants, including about 100 BBDP participants per year who donate their brains and have comprehensive neuropathological assessments after they die. Our Affiliated APOE Program will include about 300 biennially assessed cognitively unimpaired APOE4 homozygotes, heterozygotes and non-carriers. Our pending APOE4/APOE2 Allelic Dose Grant will include about 300 biennially assessed age and APOE genotype-stratified participants with each of the six major APOE genotypes, including highest risk APOE4/4 and lowest risk APOE2/2 genotypes and those who remain cognitively unimpaired at older ages despite their genetic risk. The CC will provide an resource of annual NACC- and NCRAD-shared data and blood samples in BBDP participants to evaluate the accuracy of BBBs for AD/ADRD to support their neuropathological validation and use in research, drug development and clinical setting. It will provide a full set of NACC and NCRAD-shared clinical, Aβ PET, tau PET and MRI data and CSF, blood and DNA samples in 50 Hispanic/Latino, 50 Native American to help confirm the accuracy and support the use of BBBs in these understudied groups. It will provide additional NACC and NCRAD-shared data, biomarkers and samples in cognitively unimpaired participants at different levels of genetic and biomarker risk to support to support the use of BBBs and other measurements in the early detection and tracking of AD, help in the evaluation of risk, resilience and resistance factors, inform the design and analysis of prevention trials. These resources will give our researchers a chance to find ways to treat and prevent AD by 2025 and address NAPA goals.

项目摘要/摘要-临床核心 亚利桑那州ADRC的临床核心(CC)是由五个招聘地点组成的联盟，提供集水区 在整个凤凰城和图森，组成了一个标准化的单位，由一个临床核心主任领导。消委会 对临床前阿尔茨海默病(AD)的研究和加速评估非常感兴趣 阿尔茨海默病预防疗法，重点是开发基于血液的生物标志物(BBB)。消委会将 提供NACC共享的统一数据集(UD)和脑图像，以及NCRAD共享的脑脊液、DNA和血液 来自约1,650个样本的样本很好地描述了我们ADRC赠款中纵向评估的研究参与者- 支持临床核心，我们的组织和慈善支持附属的大脑和身体捐赠 计划(BBDP)及其附属APOE计划，以及我们即将获得NIA拨款支持的APOE4/APOE2等位基因 剂量队列。我们的临床核心将包括每年评估的550例痴呆症、轻度认知障碍(MCI) 和认知未受损的参与者，包括约300名参加我们BBDP的人，约200人来自 亚利桑那州西班牙裔/拉丁裔和美洲原住民社区的代表性不足，以及那些最初在认知上 我们附属APOE计划和APOE4/APOE2等位基因剂量队列中的未受损参与者在他们 MCI和痴呆症的进展。我们的附属BBDP将包括大约500名额外的BBDP参与者 有和没有阿尔茨海默病、帕金森病和相关痴呆(ADRD)的临床表现，提供 来自约800名BBDP参与者的数据和样本的综合资源，其中包括约100名BBDP 每年捐献大脑并进行全面神经病理评估的参与者 他们会死的。我们附属的APOE计划将包括大约300项每两年评估一次的认知未受损的APOE4 纯合子、杂合子和非携带者。我们即将推出的APOE4/APOE2等位剂量补助将包括 每两年评估300名年龄和载脂蛋白E基因分层的参与者，其中六个主要载脂蛋白E 基因类型，包括最高风险的APOE4/4和最低风险的APOE2/2基因类型以及那些 尽管有遗传风险，但在较年长的时候认知能力没有受损。CC将提供每年NACC的资源- 和NCRAD-共享BBDP参与者的数据和血液样本，以评估BBBS对 AD/ADRD支持其神经病理学验证和在研究、药物开发和临床中的使用 布景。它将提供全套NACC和NCRAD共享的临床、Aβ正电子发射计算机断层扫描、Tau正电子发射计算机断层扫描和核磁共振数据和脑脊液， 对50名西班牙裔/拉丁裔和50名美国原住民的血液和DNA样本进行检测，以帮助确认准确性并支持 在这些未充分研究的群体中使用BBBS。它将提供更多NACC和NCRAD共享的数据、生物标志物 以及不同遗传和生物标记物风险水平的认知未受损参与者的样本支持 支持使用BBBS和其他测量方法对AD进行早期发现和跟踪，帮助评估 风险、复原力和抵抗力因素，为预防试验的设计和分析提供信息。这些资源 将使我们的研究人员有机会找到到2025年治疗和预防AD的方法，并实现国家适应行动方案的目标。