Alzheimer's Disease Neuroimaging Initiative

描述（由申请人提供）：我们建议在计划接受[F-i8]2-氟-2-脱氧葡萄糖（FDG） PET扫描的ADNI受试者亚群中，通过正电子发射断层扫描（PET）和匹兹堡化合物B （PIB）对淀粉样斑块负荷进行成像，作为资助的五年ADNI成像方案的一部分，来补充阿尔茨海默病神经成像倡议（ADNI）研究。神经病理学上，阿尔茨海默病（AD）是由淀粉样蛋白（Ap）组成的斑块的存在所定义的。仅凭这一点，就可以确定活着的阿尔茨海默病患者的病理，因为它可以细化早期诊断和识别症状前病理，作为一种生物标志物。此外，新的抗淀粉样蛋白疗法的最佳发展将需要一种监测脑淀粉样蛋白负荷的手段。在对参加ADNI FDG PET成像方案的受试者进行FDG PET扫描之前，将对24名对照组、48名轻度认知障碍（MCI）和24名AD受试者在16个ADNI PET部位进行PIB PET扫描。对照和MCI受试者将在入组（基线）、12、24和36个月时进行扫描。AD受试者将在基线、12个月和24个月时进行扫描。这些补充PIB PET研究将充分利用ADNI资源，包括加州大学圣地亚哥分校ADNI协调中心的行政支持，以及现有的MR和PET扫描仪质量控制程序和数据存储、管理和检索程序。匹兹堡大学的研究人员将使用已建立的基于图像的方法分析PIB PET数据，并将结果发布在ADNI神经成像实验室（LONI）服务器上以供传播。拟议的补充PIB PET研究将提供这些受试者中AP斑块结合的患病率和数量的独特但互补的功能成像数据，并进一步扩展最初ADNI资助的目标、假设和具体目的。PIB PET补充的具体目的包括：i)确定对照组、MCI和AD受试者中PIB滞留量和区域分布的差异，并将这些差异与ADNI研究者收集的同一受试者的认知、葡萄糖代谢和结构MR测量结果联系起来；2)确定对照组、MCI和AD受试者中PIB保留的数量和区域分布如何随时间变化，并将这些变化与ADNI研究者在同一受试者中测定的认知、葡萄糖代谢和结构MR变化测量相关联；3)将全脑和个体感兴趣区域的PIB保留与血液、尿液和脑脊液生物标志物相关联。

DESCRIPTION (provided by applicant): We propose to supplement the Alzheimer's Disease Neuroimaging Initiative (ADNI) study by imaging amyloid plaque burden with positron emission tomography (PET) and Pittsburgh Compound B (PIB) in a subset of ADNI subjects who are scheduled to receive [F-i8]2-fluoro-2-deoxyglucose (FDG) PET scans as part of the funded five year ADNI imaging protocol. Neuropathologically, Alzheimer's disease (AD) is defined by the presence of plaques composed of the amyloid-beta (Ap) protein. This alone makes identification of AD pathology in living subjects an important goal because it could allow refinement of early diagnosis and identification of pre-symptomatic pathology for use as a biomarker. In addition, the optimal development of new anti-amyloid therapies will require a means to monitor brain amyloid load. PIB PET scans will be conducted in 24 control, 48 mild cognitive impairment (MCI), and 24 AD subjects at 16 ADNI PET sites immediately prior to FDG PET scans in subjects enrolled in the ADNI FDG PET imaging protocol. Controls and MCI subjects will be scanned at entry (baseline), 12, 24, and 36 months. AD subjects will be scanned at baseline, 12 and 24 months. These supplementary PIB PET studies will make full use of ADNI resources including administrative support of the ADNI Coordinating Center at UC San Diego as well as of existing MR and PET scanner quality control programs and data storage, management, and retrieval programs. Investigators at the University of Pittsburgh will analyze the PIB PET data using established image-based methods and post the results on the ADNI Laboratory of Neuroimaging (LONI) server for dissemination. The proposed supplemental PIB PET studies will provide unique, yet complementary, functional imaging data of the prevalence and amount of AP plaque binding in these subjects and further extend the objectives, hypotheses, and specific aims of the original ADNI grant. Specific Aims of the PIB PET Supplement include: i) determine differences in the quantity and regional distribution of PIB retention in control, MCI, and AD subjects and relate these differences to cognitive, glucose metabolic, and structural MR measures in the same subjects collected by ADNI investigators; 2) determine how the quantity and regional distribution of PIB retention changes over time in control, MCI, and AD subjects and relate these changes to cognitive, glucose metabolic, and structural MR change measures determined in the same subjects by ADNI investigators; and 3) correlate PIB retention in whole brain and individual regionsof-interest to blood, urine and CSF biomarkers.