Dominantly Inherited Alzheimer Network: Imaging Core

核心G：映像摘要 迄今在主要遗传性阿尔茨海默病网络(DIAN)参与者中收集的成像数据集 对于阿尔茨海默病(AD)的研究来说，这是一个非常有价值的资源。它已经支撑了横截面 分析PET和MRI数据以建立常染色体显性遗传性AD生物标志物成像的时间表 (Adad)。有了这次续订申请，DIAN成像核心将继续获得和分析纵向 成像数据与临床、心理测量和脑脊液(CSF)生物标记物完全集成，以及 将允许进行突变特定的基因型-表型分析。 成像核心将负责采集、质量控制和分析核磁共振和正电子发射计算机断层扫描 为DIAN做神经成像。AD导致突变的携带者及其非携带者兄弟姐妹被登记并 紧随其后的是临床核心，通过国际DIAN表演站点。参赛者将接受 结构和功能磁共振成像、淀粉样蛋白PET、tau PET和代谢PET成像，每两年一次 以及他们的临床访问。源成像数据和后处理数据将可用于协作和 由外部调查人员提供，并将由信息学和生物统计核心分发。 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。因为没有单一的示踪剂具有到达所有站点的国际分布，所以每个站点都 为三个tau PET示踪剂分配了一个。使用多个跟踪器可最大化DIAN站点的数量， 可以进行tau PET成像。在研究中加入多个示踪剂可以降低选择其中一个的风险 对于如此大型的国际独特参与者研究的示踪剂。大约三分之一的参与者将接受 用每个示踪剂进行成像。我们认识到在同一项研究中使用多个示踪剂的局限性，并 已采取措施将这种风险降至最低。根据我们的初步工作，每个示踪器都独立供电 发现显著影响(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，一个候选示踪剂是 不合适的(即THK-5351与单胺氧化酶B44结合)，将用另一种取代。在整个过程中 除了该提案，我们还将与制药合作伙伴合作，以加强示踪剂在更广泛的国际上的可获得性 网络。

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.