Neuropathology Core

神经病理学核心

• 批准号: 10264664
• 负责人: LEE-WAY JIN
• 金额: $ 32.71万
• 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/10264664
• 关键词: African American; Aging; Alzheimer' s Disease; Animal Model; Applications Grants; Asians; 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; Diagnostic; Disease; Education; Education and Outreach; Educational Activities; Elderly; Faculty; Fostering; Funding; Future; General Population; Goals; Gold; Grant; Heterogeneity; Hispanics; 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; 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.

项目摘要/摘要 - 神经病理核心 UCD ADRC的总体目标是了解解释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，主要 神经病理学核心（NPC）的任务是以多重形式评估和量化脑损伤 病理学对于个人认知能力的最精确和相关特征必不可少。提供 甚至更深的病理表型，NPC通过 实施数字病理学并开发机器学习工作流以进行定量区域分析。 这些NPC数据与全面的认知评估，大脑成像和其他生物学联系在一起时 其他ADRC核心产生的标记将有助于对保护/风险因素的新理解 大脑衰老和痴呆过程。我们的NPC在（1）中是独一无二的。 由临床核心（CC）维持的多种多样的多种族/种族纵向队列，重点是 早期疾病/早期病理，（2）从认知轨迹的病例中收集组织样本 通过临床，成像经过证明和病理确认的脑血管损伤的修饰，（3） 来自少数族裔参与者的大量样本和数据集（39位西班牙裔/拉丁裔，18个亚洲人和52 非洲裔美国人）产生了很高的影响出版物。与其他ADRC合作 我们已经建立，维护和增强了我们的研究基础架构，积累了独特的数据集， 高质量的样本以及临床病理，转化和基础研究合作的经验。 使用后验尸的研究继续发现痴呆症的新原因和痴呆症的因素 大脑标本，丰富生物标志物的痴呆症风险。现代神经病理技术 （例如，我们的机器学习研究）与新的分子工具（例如我们的Quanterix系统 生物标志物核）有可能促进我们对疾病发病机理的理解， 因此，提供了一定程度的精度来锚定通常观察到的临床和生物异质性 失智。此外，神经病理学在未来的干预措施中起着核心作用，因为验证后的诊断是 建立生物标志物适用性和实验干预功效的黄金标准。因此，我们 设想NPC将继续成为多组分研究项目的中心参与者，以寻找 痴呆症治疗的新途径。因此，NPC领导将继续与研究人员建立联系 在升级核心诊断能力的同时进行多学科研究 使用新方法的多种脑损伤途径。