Multimodal Disease Characterization Core

多模式疾病表征核心

• 批准号: 10494773
• 负责人: Afonso C Silva
• 金额: $ 75.33万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10494773
• 关键词: Acclimatization; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease patient; Alzheimer' s disease therapeutic; Amyloid; Amyloid beta-Protein; Anatomy; Anesthesia procedures; Animals; Behavioral; Biological Assay; Biological Markers; Birth; Blood; Blood - brain barrier anatomy; Brain; Callithrix; Cerebrospinal Fluid; Clinical; Cognitive; Conscious; Custom; Data; Data Collection; Disease; Disease Progression; Early Onset Alzheimer Disease; Ensure; Evaluation; Functional Magnetic Resonance Imaging; Funding; Generations; Genetic Risk; Human; Image; Infant; Knowledge; Liquid substance; Longevity; Magnetic Resonance Imaging; Measurement; Measures; Methods; Mission; Modeling; Motor; Onset of illness; Outcome; Pathogenicity; Pathologic; Phenotype; Plasma; Positron-Emission Tomography; Proteomics; Protocols documentation; Recovery; Research; Research Project Grants; Rest; Sampling; Senile Plaques; Serum; Staging; Standardization; Structure; Testing; Therapeutic Intervention; Time; Translational Research; Ultrasonography; Validation; Work; arterial stiffness; awake; base; behavior test; clinical biomarkers; cognitive testing; cytokine; data acquisition; data analysis pipeline; early onset; experimental study; fluorodeoxyglucose positron emission tomography; glucose metabolism; healthy aging; multimodality; neuroimaging; new therapeutic target; novel therapeutics; restraint; risk variant; serial imaging; tau Proteins; tau aggregation; tau-1; trait; transcriptomics; translational study; β-amyloid burden

PROJECT SUMMARY MULTIMODAL DISEASE CHARACTERIZATION CORE The mission of the Multimodal Disease Characterization Core (MDCC) is to develop, optimize, and validate a standardized multimodal testing pipeline to conduct the longitudinal assessment of functional, behavioral, and clinical biomarkers capable of establishing healthy aging trajectories and identify divergent phenotypic changes to corroborate the early-onset (EOAD) and late-onset (LOAD) marmoset models and establish best practices and protocols. The MDCC will support the longitudinal comprehensive phenotypic characterization of the marmoset models of Alzheimer's disease (AD) developed in the Research Projects. The MDCC will optimize state-of-the-art protocols in neuroimaging, behavioral testing and cognitive assessment, and biomarkers assays to perform longitudinal evaluations from birth through the emergence of disease onset. Neuroimaging protocols will follow the ADNI-3 data acquisition and processing pipeline to obtain PET measures of amyloid, pathological tau, and glucose metabolism, MRI measures of brain structure, and measures of task-free and task-based functional MRI. The MDCC will also optimize ultrasound imaging protocols to assess arterial stiffness and blood velocity. A behavioral testing pipeline will be developed, optimized, and validated, and will be used to characterize aging phenotypes in marmosets with test-retest reliability. Finally, the MDCC will perform measurements of fluid-based blood serum and cerebrospinal fluid biomarkers, and correlate them with functional, behavioral, cognitive, and neuroimaging changes. Work in the MDCC work will lead to the characterization and validation of marmoset models of AD, which will be invaluable in translational research to elucidate the pathogenic mechanisms of AD and contribute to developing new therapeutics for AD.

多模式疾病表征核心项目总结 多模式疾病表征核心（MDCC）的使命是开发、优化和验证 标准化的多模态测试管道，以进行功能，行为和 能够建立健康衰老轨迹并识别不同表型变化的临床生物标志物 证实早发性（EOAD）和迟发性（LOAD）绒猴模型，并建立最佳实践 和协议。MDCC将支持纵向全面的表型表征 研究项目中开发的阿尔茨海默病（AD）绒猴模型。MDCC将优化 神经影像学、行为测试和认知评估以及生物标志物方面的最新方案 从出生到疾病发作的出现进行纵向评估的分析。神经影像 协议将遵循ADNI-3数据采集和处理管道以获得淀粉样蛋白的PET测量， 病理性tau和葡萄糖代谢，脑结构的MRI测量，以及无任务和 基于任务的功能性MRI MDCC还将优化超声成像协议，以评估动脉 硬度和血流速度。将开发、优化和验证行为测试管道， 可以用来表征老化表型在绒猴与重测信度。最后，MDCC将 进行基于液体的血清和脑脊液生物标志物的测量，并将它们与 功能、行为、认知和神经影像学变化。MDCC的工作将导致 AD的绒猴模型的表征和验证，这将是非常宝贵的转化研究， 阐明AD的发病机制，为开发AD的新治疗药物做出贡献。