The natural history of AB accumulation in preclinical AD

临床前 AD 中 AB 积累的自然史

• 批准号: 8287320
• 负责人: JOHN MORRIS
• 金额: $ 55.23万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8287320
• 关键词: APP-PS1; Adult; Adult Children; Affect; Age; Age-Years; Alleles; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Atrophic; Binding; Biological; Biological Markers; Biometry; Brain; Cerebrospinal Fluid; Cerebrum; Cessation of life; Chronology; Clinical; Cognitive; Conduct Clinical Trials; Data; Data Analyses; Deposition; Derivation procedure; Fostering; Functional disorder; Funding; Future; Genotype; Growth; Histologic; Image; Impaired cognition; Incidence; Individual; Instruction; Intervention; Knowledge; Life; Measures; Mediating; Natural History; Occupations; Participant; Peptides; Performance; Persons; Pittsburgh Compound-B; Positioning Attribute; Positron-Emission Tomography; Prevention; Primary Prevention; Program Research Project Grants; Property; Recording of previous events; Research; Resources; Sample Size; Scanning; Senile Plaques; Signal Transduction; Source; Staging; Testing; Time; Tracer; Transgenic Mice; base; benzothiazole; brain volume; cognitive reserve; cohort; data management; design; high risk; in vivo; middle age; neuropathology; pre-clinical

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.

项目 1 旨在表征纤维状脑淀粉样蛋白 (AP) 随着年龄增长的积累情况 范围从Ap沉积出现的时间到Ap水平接近有症状的时间 阿尔茨海默病（AD）。项目 1 提出在队列中进行纵向 [^^C] PIB 成像研究 成人儿童研究（ACS）。每两年将对所有 ACS 参与者进行 PET PIB 扫描。这 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取有助于和促进设计的数据 开展抗Ap疗法用于一级预防症状性AD的临床试验。在 特别是，它旨在帮助确定干预此类试验的最佳时间。 具体目标是： 1. 每 2 年对认知正常的 ACS 参与者进行纵向 ["C] PIB PET 扫描，以识别 从无或极少纤维状 Ajj 沉积到明显 AP 积累的转化率，定义为 通过 PIB >0.18 的平均皮质结合电位 (MCBP)，并确定该速率是否受到影响 根据年龄、APOE 基因型和父母的 AD 病史。 2. 确定 ACS 参与者（均患有 基线时有明显的 Ap 沉积 [^^C] PIB PET 扫描，而那些缺乏 Ap 沉积的患者 基线。 3. 检查认知和大脑储备变量的关联和相互作用（例如，归一化整体 脑容量；局部萎缩；职业;教育程度）与纵向认知 有或没有 Ap 积累的参与者在临床核心中获得的表现。 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，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）、生物标志物（例如，项目 1 参与者的 AP 成像中 AP42 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） 该计划项目的核心 授予。