The natural history of AB accumulation in preclinical AD

项目1旨在描述随着年龄的增长，纤维状脑淀粉样蛋白β（AP）的积累 范围从Ap沉积开始的时间到Ap水平接近有症状的Ap水平的时间。 阿尔茨海默病（AD）。项目1提出了一项纵向[^^C] PIB成像研究， 成人儿童研究（ACS）。将每两年对所有ACS参与者进行PET PIB扫描。的 获得的数据将极大地扩展关于临床前AD和Ap临床相关性的知识， 积累这项工作的长期目标是获得数据，将促进和促进设计 以及进行抗Ap疗法用于症状性AD的一级预防的临床试验。在 特别是，它旨在帮助确定在这种试验中进行干预的最佳时间。 具体目标是： 1.在认知正常的ACS参与者中每2年进行一次纵向[“C”] PIB PET扫描，以确定 从没有或最小的纤维状Ajj沉积到可感知的AP积累的转化率，定义为 PIB的平均皮质结合电位（MCBP）>0.18，并确定该速率是否受到影响 根据年龄、APOE基因型和父母AD病史。 2.确定ACS参与者中Ap蓄积的变化率和轨迹， 在基线[^^C] PIB PET扫描时可观察到Ap沉积， 基线。 3.检查认知和大脑储备变量的关联和相互作用（例如，正规化整体 脑容量;局部萎缩;职业;教育程度）与纵向认知功能 在临床核心中获得的有和无Ap蓄积的受试者的性能。 4.将项目1的调查结果与项目2、3和4的适当数据相关联， 给药（例如，预算监督）、临床（例如，参与者来源;纵向临床和 认知数据），生物标志物（例如，项目1参与者中AP 42的脑脊液水平， 存款），以及数据管理和生物统计学（例如，数据分析）本项目的核心 格兰特.

Project 1 aims to characterize the accumulation of fibrillar cerebral amyloid-beta (AP) over the age range from the time of onset of Ap deposits to the time when Ap levels approximate those of symptomatic Alzheimer's disease (AD). Project 1 proposes a longitudinal [^^C] PIB imaging study in the cohort of the Adult Children Study (ACS). PET PIB scans will be done on ail ACS participants every two years. The data to be obtained will greatly expand knowledge about preclinical AD and the clinical correlates of Ap accumulation. The long term objective of this effort is to obtain data that will facilitate and foster the design and conduct of clinical trials of anti-Ap therapies for the primary prevention of symptomatic AD. In particular, it aims to help determine the optimal time for intervention in such a trial. Specific Aims are: 1. Obtain longitudinal ["C] PIB PET scans every 2 years in cognitively normal ACS participants to identify the conversion rate from no or minimal fibrillar Ajj deposition to appreciable AP accumulation, defined by mean cortical binding potential (MCBP) for PIB >0.18, and determine whether this rate is affected by age, APOE genotype, and parental history of AD. 2. Determine the rate and trajectory of change in Ap accumulation in ACS participants, both those with appreciable Ap deposits at their baseline [^^C] PIB PET scan and those lacking Ap deposits at baseline. 3. Examine associations and interactions of cognitive and brain reserve variables (e.g., normalized whole brain volume; regional atrophy; occupation; educational attainment) with longitudinal cognitive performance, obtained in the Clinical Core, in participants with and without Ap accumulation. 4. Correlate findings from Project 1 with appropriate data from Projects 2, 3, and 4 and utilize the Administration (e.g., budgetary oversight), Clinical (e.g., source of participants; longitudinal clinical and cognitive data), Biomarker (e.g., cerebrospinal fluid levels of AP42 in Project 1 participants imaged for Ap deposits), and Data Management and Biostatistics (e.g., data analyses) Cores of this program project grant.