Dominantly Inherited Alzheimer Network: Imaging Core

显性遗传阿尔茨海默病网络：成像核心

• 批准号: 10462562
• 负责人: Tammie Lee Smith Benzinger
• 金额: $ 95.31万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10462562
• 关键词: Affect; Alzheimer' s Disease; Alzheimer' s disease patient; Amyloid; Amyloid deposition; Appearance; Binding; Biological Markers; Biostatistics Core; Brain; Brain imaging; Cerebrospinal Fluid; Cerebrum; Clinical; Clinical Trials Design; Cross-Sectional Studies; Cyclotrons; DNA Sequence Alteration; Data; Data Analyses; Data Set; Deposition; Diffusion; Diffusion Magnetic Resonance Imaging; Enrollment; Ensure; Evaluation; Functional Magnetic Resonance Imaging; Future; Genotype; Good Clinical Practice; Guidelines; Hemorrhage; Image; Imaging Techniques; Immunohistochemistry; Impaired cognition; Inflammation; Informatics; Inherited; International; Late Onset Alzheimer Disease; Magnetic Resonance Imaging; Measurement; Measures; Medical Genetics; Metabolic; Methods; Monoamine Oxidase; Mutation; Nerve Degeneration; Neurofibrillary Tangles; Neuroimmune; Neurons; Participant; Pharmacologic Substance; Phenotype; Pittsburgh Compound-B; Positron-Emission Tomography; Process; Production; Protocols documentation; Proxy; Psychometrics; Quality Control; Radiation Dose Unit; Reproducibility; Research; Research Personnel; Resources; Rest; Risk; Scanning; Siblings; Site; Source; Standardization; Synapses; Techniques; Testing; TimeLine; Tracer; Update; Visit; Work; arterial spin labeling; autosomal dominant Alzheimer' s disease; base; cohort; computerized data processing; density; disease-causing mutation; image processing; imaging approach; imaging biomarker; improved; indexing; innovation; mutation carrier; neuroimaging; neuroinflammation; neuropathology; novel; performance site; perfusion imaging; pre-clinical; quality assurance; regional atrophy; repository; risk minimization; serial imaging; spectrograph; tau Proteins; tau aggregation; white matter; β-amyloid burden

Core G: Imaging Summary The imaging data set collected in the Dominantly Inherited Alzheimer Network (DIAN) participants to date represents a highly valuable resource for Alzheimer's disease (AD) research. It has supported cross sectional analysis of PET and MRI data to develop a timeline for imaging biomarkers in autosomal dominant AD (ADAD). With this renewal application, the DIAN Imaging Core will continue to obtain and analyze longitudinal imaging data that is fully integrated with clinical, psychometric and cerebrospinal fluid (CSF) biomarkers, and will allow for mutation-specific genotype-phenotype analysis. Imaging Core will be responsible for the acquisition, quality control, and analysis of the MRI and PET neuroimaging for DIAN. Carriers of AD-causing mutations and their non-carrier siblings are enrolled and followed in the Clinical Core through the international DIAN performance sites. Participants will undergo structural and functional MRI, amyloid PET, tau PET, and metabolic PET imaging every 2 years, in conjunction with their clinical visits. The source imaging data and post-processed data will be available to collaborating and outside investigators and will be distributed by the Informatics and Biostatistics cores. For tau PET, we will now obtain scans with the tracers [18F]-MK-6240, [18F]-AV-1451 (aka Flortaucipir, T807), and [18F]-PI-2620. Because no single tracer has the international distribution to reach all sites, each site is assigned one for the three tau PET tracers. Using multiple tracers maximizes the number of DIAN sites that can perform tau PET imaging. Including multiple tracers across the study diminishes the risk of choosing one tracer for such a large, international study of unique participants. Approximately 1/3 of participants will undergo imaging with each tracer. We recognize the limitations of using multiple tracers in the same study and have taken steps to minimize this risk. Based upon our preliminary work, each tracer is independently powered to detect significant effects (see Project 2, Approach). Further, our current proposal is adaptive. If our immunohistochemistry and autoradiographic work (Project 2) demonstrates that one candidate tracer is unsuitable (i.e. THK-5351 binding to monoamine oxidase B44), it will be replaced with another. Over the course of the proposal we will also work with Pharma partners to strengthen tracer availability to a wider international network.

核心G：成像总结 迄今为止，在显性遗传阿尔茨海默病网络（DIAN）参与者中收集的成像数据集 是阿尔茨海默病（AD）研究的非常有价值的资源。它支持横截面 分析PET和MRI数据，为常染色体显性AD的成像生物标志物制定时间轴 （ADAD）。通过此次更新申请，DIAN Imaging Core将继续获取和分析纵向 与临床、心理测量和脑脊液（CSF）生物标志物完全整合的成像数据，以及 将允许突变特异性基因型-表型分析。 成像中心将负责MRI和PET的采集、质量控制和分析 神经影像学检查招募AD致突变携带者及其非携带者兄弟姐妹， 通过国际DIAN性能研究中心在临床核心中进行随访。参与者将经历 每2年进行一次结构和功能MRI、淀粉样蛋白PET、tau PET和代谢PET成像，同时 他们的临床访问。源成像数据和后处理数据将可用于协作和 外部研究者，并将由信息学和生物统计学核心分发。 对于tau PET，我们现在将使用示踪剂[18F]-MK-6240、[18F]-AV-1451（又名Flortaucipir，T807）进行扫描， 和[18F]-PI-2620。由于没有一种示踪剂具有到达所有地点的国际分布， 三个tau PET示踪剂分配一个。使用多个示踪剂可以最大限度地增加DIAN站点的数量， 可以进行tau PET成像。在整个研究中包括多个示踪剂可以降低选择一个示踪剂的风险 追踪这样一个大型的，独特的参与者的国际研究。大约1/3的参与者将接受 每种示踪剂的成像。我们认识到在同一研究中使用多种示踪剂的局限性， 采取措施尽量减少这种风险。根据我们的初步工作，每个示踪剂是独立供电， 检测显著影响（见项目2，方法）。此外，我们目前的建议是适应性的。如果我们的 免疫组织化学和放射自显影工作（项目2）表明，一种候选示踪剂是 如果不合适（即THK-5351与单胺氧化酶B44结合），则将用另一种替代。过程中 我们还将与制药合作伙伴合作，加强示踪剂在更广泛的国际范围内的可用性。 网络