The natural history of AB accumulation in preclinical AD

临床前 AD 中 AB 积累的自然史

• 批准号: 8522085
• 负责人: JOHN MORRIS
• 金额: $ 6.6万
• 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: 2005-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8522085
• 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旨在表征年龄段纤维脑淀粉样蛋白β（AP）的积累 从AP沉积发作到AP水平近似有症状的时间范围 阿尔茨海默氏病（AD）。项目1提出了一项纵向[^^ c] PIB成像研究 成人儿童学习（ACS）。 PET PIB扫描将每两年对AIL ACS参与者进行一次。这 要获得的数据将大大扩展有关临床前AD的知识和AP的临床相关性 积累。这项工作的长期目标是获取可以促进和促进设计的数据 并进行抗AP疗法的临床试验，以初级预防症状AD。在 特别是，它旨在帮助确定这种试验中干预的最佳时间。 具体目的是： 1。在认知正常的ACS参与者中获取每2年的纵向[C] PIB PET扫描 从NO或最小纤维AJJ沉积到明显的AP积累的转化率，定义 PIB> 0.18的平均皮质结合势（MCBP），并确定是否影响此速率 按年龄，APOE基因型和AD的父母历史。 2。确定ACS参与者中AP积累变化的速率和轨迹 在其基线[^^ c] PIB PET扫描和缺乏AP沉积的基线的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，整体归一化 大脑体积；区域萎缩；职业;具有纵向认知的教育成就） 在临床核心中获得的性能，在有AP积累和没有AP的参与者中获得。 4。将项目1的发现与项目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，参与者的来源；纵向临床和 认知数据），生物标志物（例如，在AP成像的项目1参与者中，AP42的脑脊液水平 存款）以及该计划项目的数据管理和生物统计学（例如，数据分析）核心 授予。