The natural history of AB accumulation in preclinical AD

项目1旨在描述大脑淀粉样β纤维蛋白(AP)随年龄的积累情况。 范围从AP沉积的开始时间到AP水平接近有症状的时间 阿尔茨海默病(AD)。项目1建议在以下人群中进行纵向[^C]PIB成像研究 成人儿童研究(ACS)。宠物PIB扫描将每两年对所有ACS参与者进行一次。这个 将获得的数据将极大地扩展关于临床前AD和AP的临床相关性的知识 积累。这项工作的长期目标是获得有助于和促进设计的数据 以及进行抗AP疗法的临床试验，以一级预防症状性AD。在……里面 特别是，它的目的是帮助确定干预此类试验的最佳时间。 具体目标是： 1.对认知正常的急性冠脉综合征患者每两年进行一次纵向PIB PET扫描，以确定 从无或最小纤维状AJJ沉积到可察觉的AP堆积的转换率，定义为 通过PIB和GT；0.18的平均皮质结合势(MCBP)，并确定这一速率是否受影响 按年龄、载脂蛋白E基因和父母AD病史分类。 2.确定急性冠脉综合征患者AP积聚的速度和变化轨迹 在基线PIB PET扫描时有明显的AP沉积，而在 基线。 3.检查认知和大脑储备变量(例如，归一化整体)之间的关联和相互作用 脑体积；区域萎缩；职业；教育程度)与纵向认知 在有和没有AP积聚的参与者中，在临床核心中获得的表现。 4.将项目1的结果与项目2、3和4的适当数据相关联，并利用 管理(例如，预算监督)、临床(例如，参与者来源；纵向临床和 认知数据)、生物标记物(例如，为AP成像的项目1参与者的脑脊液AP42水平 数据管理和生物统计(例如，数据分析)这一方案项目的核心 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.