AMYLOID IMAGING IN THE ADULT CHILDREN STUDY

成年儿童研究中的淀粉样蛋白成像

• 批准号: 7874455
• 负责人: JOHN MORRIS
• 金额: $ 57.61万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7874455
• 关键词: 6-hydroxybenzothiazole; Adult; Adult Children; Affinity; Age; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Amyloid Proteins; Amyloid deposition; Autopsy; Back; Binding; Biological; Biological Markers; Brain; Brain Injuries; Brain imaging; Cells; Child; Clinical; Clinical Data; Cognitive; Correlation Studies; Data; Dementia; Deposition; Diagnosis; Enrollment; Evaluation; Family history of; Funding; Human; Image; In Vitro; Individual; Intervention; Learning; Measures; Methods; Natural History; Neuronal Dysfunction; Parents; Participant; Patients; Performance; Personality; Population; Positron-Emission Tomography; Preparation; Prevalence; Principal Investigator; Psychometrics; Radiolabeled; Recruitment Activity; Risk; Role; Senile Plaques; Staging; Testing; Time; Tracer; Transgenic Mice; Universities; abeta accumulation; amyloid imaging; cohort; design; early onset; in vivo; lifetime risk; longitudinal course; mouse model; pre-clinical; programs; radiotracer; uptake

We hypothesize that Alzheimer's disease (AD) has a preclinical stage in which elevated levels of brain amyloid protein and accumulation of beta-amyloid deposits foreshadow the gradual onset of neuronal dysfunction, cell loss and dementia. While the exact role of amyloid in the initiation of brain damage is still unclear, it is clear that clarifying the exact timing of amyloid plaque deposition that precede AD would be extremely helpful in fully understanding the biological origins of AD and to assist in the design of appropriate interventions. This project will use a new method for the in vivo imaging of amyloid plaques in the human brain. Developed at the University of Pittsburgh, [11C]PIB has very high affinity for amyloid plaques with in vitro preparations and binds rapidly to amyloid plaques in a transgenic mouse model of amyloid deposits. We have implemented this method and demonstrated much greater cortical uptake in older participants diagnosed with DAT compared with nondemented control participants. In this project, 240 participants between the ages of 45 and 74 y will be recruited and undergo baseline imaging with PET and [11C]PIB for calculation of amyloid plaque binding. In each decade (45 - 54 y, 55 - 64 y, and 65 - 74 y) 40 participants with at least one biologic parent with DAT (age at onset, or AAO, <80y) and 40 participants whom neither parent has/had DAT (parents must be >70y) will be studied. In addition, we will re-image subjects with [11C]PIB after a three year interval to determine the longitudinal course of amyloid binding in these two cohorts. With this data we will achieve four specific aims: 1) In Years 01 - 03, we will measure and compare cortical [11C]PIB uptake in 120 ACS participants with a parent with DAT and in 120 participants without a parent with DAT. 2) We will correlate cortical [11C]PIB uptake with specific measures of cognitive performance, including presence and magnitude of learning effects, and with personality measures. 3) We will test for correlations between cortical [11C]PIB uptake and CSF biomarkers (Project 2), and between cortical [11C]PIB uptake and neuroanatomic biomarkers (Project 4). 4) In Years 04 and 05, we will repeat PET [11C]PIB imaging on participants enrolled in Years 01 and 02, respectively. By comparing the cortical [11C]PIB uptake at these two different time-points three years apart, we will be able to assess the ACS cohorts longitudinally to determine the natural history of [11C]PIB binding and its potential for preclinical detection of AD.

我们假设阿尔茨海默氏病（AD）具有临床前阶段，其中脑淀粉样蛋白的水平升高和β-淀粉样蛋白沉积物的积累预示了神经元功能障碍，细胞丧失和痴呆症的逐渐发作。尽管淀粉样蛋白在开始脑损伤中的确切作用尚不清楚，但很明显，阐明AD之前的淀粉样蛋白斑块沉积的确切时机将非常有助于充分理解AD的生物学起源并协助设计适当的干预措施。 该项目将使用一种新方法来对人脑中淀粉样蛋白斑块进行体内成像。 [11C] PIB在匹兹堡大学开发，对淀粉样蛋白斑块具有非常高的亲和力，并在体外制剂中具有很高的亲和力，并且在淀粉样蛋白沉积物的转基因小鼠模型中与淀粉样蛋白斑块迅速结合。我们已经实施了这种方法，并证明了与非对照参与者相比，被诊断为DAT的老年参与者的皮质摄取要大得多。在这个项目中，将招募45至74岁之间的240名参与者，并使用PET和[11C] PIB进行基线成像，以计算淀粉样蛋白斑块结合。在每十年（45-54 y，55-64 y和65-74 y）中，有至少一名具有DAT的生物父母的参与者（年龄在一开始，或AAO，<80y，<80y），而父母都不知道DAT（父母必须> 70y）的40名参与者将被研究。此外，我们将在三年间隔后与[11C] PIB重新形象受试者，以确定这两个队列中淀粉样蛋白结合的纵向过程。通过这些数据，我们将实现四个具体目标：1）在01-03年中，我们将测量和比较120个ACS参与者的皮质[11C] PIB吸收，其中包括DAT的父母，而在没有父母的120名参与者中，有120名参与者。 2）我们将将皮质[11C] PIB的吸收与认知表现的特定度量相关联，包括学习效应的存在和幅度以及人格量度。 3）我们将测试皮质[11C] PIB摄取与CSF生物标志物（项目2）之间的相关性，以及皮质[11C] PIB摄取和神经解剖生物标志物（项目4）之间的相关性。 4）在04年和05年中，我们将分别重复PET [11C] PIB成像为01和02年的参与者。通过比较皮质 [11C] PIB在这两个不同的时间点相隔三年的时间内吸收，我们将能够纵向评估ACS队列，以确定[11C] PIB结合的自然历史及其对AD的临床前检测的潜力。