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: 6989336
• 负责人: JOHN MORRIS
• 金额: $ 22.57万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6989336
• 关键词: Alzheimer' s disease; amyloid proteins; bioimaging /biomedical imaging; biomarker; carbon; cerebrospinal fluid; clinical research; cognition; disease /disorder proneness /risk; human middle age (35-64); human old age (65+); human subject; longitudinal human study; neuropathology; personality; positron emission tomography; psychometrics; radiotracer

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病(AD)有一个临床前阶段，在这个阶段，脑淀粉样蛋白水平的升高和β-淀粉样蛋白沉积的积累预示着神经元功能障碍、细胞丢失和痴呆的逐渐发病。虽然淀粉样蛋白在启动脑损伤中的确切作用尚不清楚，但很明显，澄清AD之前淀粉样斑块沉积的确切时间将非常有助于全面了解AD的生物学起源，并有助于设计适当的干预措施。 该项目将使用一种新的方法对人脑中的淀粉样斑块进行体内成像。匹兹堡大学开发的[11C]PIB与体外制备的淀粉样斑块具有非常高的亲和力，并在淀粉样沉积的转基因小鼠模型中快速与淀粉样斑块结合。我们已经实施了这种方法，并证明与非痴呆对照参与者相比，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，240名年龄在45岁到74岁之间的参与者将被招募，并接受PET和[11C]PIB的基线成像，以计算淀粉样斑块结合。在每十年(45-54岁、55-岁和65-74岁)中，40名至少有一位亲生父母患有DAT的参与者(发病年龄为80岁)和40名父母都没有/有DAT的参与者(父母必须是70岁)将被纳入研究。此外，我们将在三年后用[11C]PIB重新成像受试者，以确定这两个队列中淀粉样蛋白结合的纵向过程。有了这些数据，我们将实现四个具体目标：1)在01-03年，我们将测量和比较120名ACS参与者和患有DAT的父母以及120名没有父母患有DAT的参与者的皮质[11C]PIB摄取。2)我们将把大脑皮层[11C]PIB摄取与认知表现的具体测量相关联，包括学习效果的存在和大小，以及人格测量。3)我们将测试皮质[11C]PIB摄取与脑脊液生物标记物之间的相关性(项目2)，以及皮质[11C]PIB摄取与神经解剖生物标记物之间的相关性(项目4)。4)在04年和05年，我们将分别对01年和02年登记的参与者重复PET[11C]PIB成像。通过比较大脑皮质 [11C]在这两个不同时间点相隔三年的PIB摄取，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临床前AD检测的潜力。