Dominantly Inherited Alzheimer Network: Imaging Core

显性遗传阿尔茨海默病网络：成像核心

• 批准号: 10225485
• 负责人: Tammie Lee Smith Benzinger
• 金额: $ 120.37万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10225485
• 关键词: Affect; Alzheimer' s Disease; Alzheimer' s disease patient; Amyloid; Amyloid deposition; Appearance; Binding; Biological Markers; Biostatistics Core; Brain; Brain imaging; Cerebrospinal Fluid; Cerebrum; Clinical; Clinical Trials Design; Cross-Sectional Studies; Cyclotrons; DNA Sequence Alteration; Data; Data Analyses; Data Set; Deposition; Diffusion; Diffusion Magnetic Resonance Imaging; Enrollment; Ensure; Evaluation; Functional Magnetic Resonance Imaging; Future; Genotype; Good Clinical Practice; Guidelines; Hemorrhage; Image; Imaging Techniques; Immunohistochemistry; Impaired cognition; Inflammation; Informatics; Inherited; International; Late Onset Alzheimer Disease; Magnetic Resonance Imaging; Measurement; Measures; Medical Genetics; Metabolic; Methods; Monoamine Oxidase; Mutation; Nerve Degeneration; Neurofibrillary Tangles; Neuroimmune; Neurons; Participant; Pharmacologic Substance; Phenotype; Pittsburgh Compound-B; Positron-Emission Tomography; Process; Production; Protocols documentation; Proxy; Psychometrics; Quality Control; Radiation Dose Unit; Reproducibility; Research; Research Personnel; Resources; Rest; Risk; Scanning; Siblings; Site; Source; Spin Labels; Standardization; Structure; Synapses; Techniques; Testing; TimeLine; Tracer; Update; Visit; Work; autosomal dominant Alzheimer' s disease; base; cohort; computerized data processing; density; disease-causing mutation; image processing; imaging approach; imaging biomarker; improved; indexing; innovation; mutation carrier; neuroimaging; neuroinflammation; neuropathology; novel; performance site; perfusion imaging; pre-clinical; quality assurance; regional atrophy; repository; risk minimization; serial imaging; spectrograph; tau Proteins; tau aggregation; white matter; β-amyloid burden

Core G: Imaging Summary The imaging data set collected in the Dominantly Inherited Alzheimer Network (DIAN) participants to date represents a highly valuable resource for Alzheimer's disease (AD) research. It has supported cross sectional analysis of PET and MRI data to develop a timeline for imaging biomarkers in autosomal dominant AD (ADAD). With this renewal application, the DIAN Imaging Core will continue to obtain and analyze longitudinal imaging data that is fully integrated with clinical, psychometric and cerebrospinal fluid (CSF) biomarkers, and will allow for mutation-specific genotype-phenotype analysis. Imaging Core will be responsible for the acquisition, quality control, and analysis of the MRI and PET neuroimaging for DIAN. Carriers of AD-causing mutations and their non-carrier siblings are enrolled and followed in the Clinical Core through the international DIAN performance sites. Participants will undergo structural and functional MRI, amyloid PET, tau PET, and metabolic PET imaging every 2 years, in conjunction with their clinical visits. The source imaging data and post-processed data will be available to collaborating and outside investigators and will be distributed by the Informatics and Biostatistics cores. For tau PET, we will now obtain scans with the tracers [18F]-MK-6240, [18F]-AV-1451 (aka Flortaucipir, T807), and [18F]-PI-2620. Because no single tracer has the international distribution to reach all sites, each site is assigned one for the three tau PET tracers. Using multiple tracers maximizes the number of DIAN sites that can perform tau PET imaging. Including multiple tracers across the study diminishes the risk of choosing one tracer for such a large, international study of unique participants. Approximately 1/3 of participants will undergo imaging with each tracer. We recognize the limitations of using multiple tracers in the same study and have taken steps to minimize this risk. Based upon our preliminary work, each tracer is independently powered to detect significant effects (see Project 2, Approach). Further, our current proposal is adaptive. If our immunohistochemistry and autoradiographic work (Project 2) demonstrates that one candidate tracer is unsuitable (i.e. THK-5351 binding to monoamine oxidase B44), it will be replaced with another. Over the course of the proposal we will also work with Pharma partners to strengthen tracer availability to a wider international network.

核心G：成像总结