Neuropathology Core

神经病理学核心

• 批准号: 10461124
• 负责人: LEE-WAY JIN
• 金额: $ 33.24万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10461124
• 关键词: African American; Aging; Alzheimer' s Disease; Animal Model; Applications Grants; Asian; Autopsy; Basic Science; Biological; Biological Markers; Brain; Brain Diseases; Brain Injuries; Brain imaging; Clinic; Clinical; Clinical Pathology; Cognitive; Collaborations; Complex; Consensus; Data; Data Set; Dementia; Detection; Diagnosis; Disease; Education; Education and Outreach; Educational Activities; Elderly; Faculty; Fostering; Funding; Future; General Population; Goals; Gold; Grant; Heterogeneity; Hispanic; Image; Impaired cognition; Individual; Infrastructure; Injury; Interdisciplinary Study; Intervention; Journals; Knowledge; Latino; Leadership; Link; Longitudinal cohort; Machine Learning; Medical Staff; Methods; Minority; Mission; Modernization; Molecular; Participant; Pathogenesis; Pathologic; Pathology; Pathway interactions; Phenotype; Play; Predictive Value; Prevention; Process; Prognosis; Publications; Reporting; Research; Research Infrastructure; Research Personnel; Research Project Grants; Resources; Risk Factors; Role; Sampling; Scientist; Services; Societies; Specimen; Standardization; Students; Study Subject; System; Techniques; Technology; Time; Tissue Banks; Tissue Sample; Tissues; Training; Translating; Translational Research; aging brain; biobank; biological heterogeneity; brain tissue; career; cerebrovascular; clinical heterogeneity; cognitive ability; cognitive testing; cohort; dementia risk; diagnostic value; digital pathology; experience; meetings; member; multi-ethnic; neuropathology; novel; racial and ethnic; symposium; tool

PROJECT SUMMARY/ABSTRACT - Neuropathology Core The overarching goal of the UCD ADRC is to understand the multiple and complex determinants that explain the heterogeneity of cognitive trajectories among diverse older adults. To help achieve this goal, the primary mission of the Neuropathology Core (NPC) is to assess and quantify brain injury in the form of multiple pathologies essential to the most precise and relevant characterization of individual cognitive ability. To provide even deeper pathological phenotypes, the NPC has leveraged and enhanced Core infrastructure by implementing digital pathology and developing machine learning workflows for quantitative regional analysis. These NPC data, when linked with comprehensive cognitive assessment, brain imaging, and other biological markers generated by other ADRC Cores will facilitate new understandings into the protective/risk factors of brain aging and dementia processes. Our NPC is unique in (1) its study subjects have been drawn from a diverse multi-ethnic/racial longitudinal cohort maintained by the Clinical Core (CC) with an emphasis on early disease/early pathology, (2) its collection of tissue samples from cases whose cognitive trajectories have been modified by clinically, imaging proven, and pathologically confirmed cerebrovascular injury and (3) its sizeable number of samples and datasets from minority participants (39 Hispanic/Latino, 18 Asian, and 52 African American) that have resulted in high impact publications. In collaboration with the other ADRC Cores, we have built, maintained, and enhanced our research infrastructure, accumulating unique datasets, high quality samples, and experience in clinic-pathological, translational, and basic research collaborations. New causes and contributing factors of dementia continue to be discovered by studies using post-mortem brain specimens, enriching the pool of biomarkers for risk of dementia. Modern neuropathology techniques (e.g., our machine learning studies) combined with new molecular tools (such as our Quanterix system within the Biomarker core) have the potential to tremendously advance our understanding of disease pathogenesis, thus providing a degree of precision to anchor the clinical and biological heterogeneity commonly observed in dementia. Moreover, neuropathology plays a central role in future interventions, as postmortem diagnosis is the gold standard to establish biomarkers applicability and the efficacy of experimental interventions. Thus, we envision the NPC will continue to be a central player in multi-component research projects in the effort to find new avenues for dementia treatment. As such, the NPC leadership will continue networking with researchers to conduct multidisciplinary research while upgrading the core diagnostic capabilities to enable detection of diverse brain injury pathways using novel methods.

项目总结/摘要-神经病理学核心 UCD ADRC的总体目标是了解解释这些问题的多重和复杂的决定因素。 不同老年人认知轨迹的异质性。为了帮助实现这一目标， 神经病理学核心（NPC）的使命是评估和量化多种形式的脑损伤 对个体认知能力的最精确和相关表征至关重要的病理学。提供 即使是更深层次的病理表型，NPC也通过以下方式利用和增强了核心基础设施： 实施数字病理学和开发用于定量区域分析的机器学习工作流程。 这些NPC数据，当与全面的认知评估，脑成像和其他生物学指标相联系时， 其他ADRC核心产生的标记将促进对保护/风险因素的新理解， 大脑老化和痴呆的过程。我们的NPC的独特之处在于：（1）它的研究对象来自一个 由临床核心（CC）维护的多样化多种族/人种纵向队列，重点是 早期疾病/早期病理学，（2）从认知轨迹具有以下特征的病例中收集组织样本： 经临床、影像学证实和病理学证实的脑血管损伤和（3）其 来自少数民族参与者的大量样本和数据集（39名西班牙裔/拉丁裔，18名亚洲人和52名 非洲裔美国人），产生了高影响力的出版物。与其他ADRC合作 核心，我们已经建立，维护和加强我们的研究基础设施，积累独特的数据集， 高质量的样本，以及临床病理学，转化和基础研究合作的经验。 通过使用尸检的研究，痴呆症的新原因和促成因素不断被发现。 大脑标本，丰富了痴呆症风险的生物标志物库。现代神经病理学技术 (e.g.,我们的机器学习研究）结合新的分子工具（如我们的Quanterix系统， 生物标志物核心）有可能极大地促进我们对疾病发病机制的理解， 从而提供了一定程度的精确度，以锚定通常在 痴呆此外，神经病理学在未来的干预中发挥着核心作用，因为死后诊断是 建立生物标志物适用性和实验干预有效性的黄金标准。因此我们 我设想，全国人大将继续在多组成部分的研究项目中发挥核心作用，努力寻找 痴呆症治疗的新途径因此，全国人大领导层将继续与研究人员建立联系 开展多学科研究，同时提升核心诊断能力， 使用新方法的多种脑损伤途径。