Neuropathology Core

项目摘要/摘要-神经病理学核心 UCD ADRC的首要目标是了解解释以下问题的多重复杂决定因素 不同老年人之间认知轨迹的异质性。为了帮助实现这一目标，主要的 神经病理学核心(NPC)的使命是评估和量化多发性脑损伤 对最精确和最相关的个人认知能力的表征至关重要的病理学。要提供 更深层次的病理表型，NPC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。 这些鼻咽癌数据，当与综合认知评估、脑成像和其他生物 其他ADRC核心生成的标记将有助于对以下保护/风险因素的新理解 大脑老化和痴呆症的过程。我们的全国人大的独特之处在于：(1)其研究对象选自 由临床核心(CC)维持的多样化的多民族/种族纵向队列，重点是 早期疾病/早期病理，(2)从认知轨迹为 经临床、影像和病理证实的脑血管损伤和(3)ITS 来自少数族裔参与者的大量样本和数据集(39名西班牙裔/拉丁裔，18名亚裔和52名 非裔美国人)，产生了影响很大的出版物。与其他亚洲发展研究中心合作 核心，我们已经建立、维护和增强了我们的研究基础设施，积累了独特的数据集， 高质量的样本，以及临床病理、翻译和基础研究方面的合作经验。 尸检研究不断发现痴呆症的新病因和致病因素 大脑样本，丰富了患痴呆症风险的生物标志物池。现代神经病理学技术 (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)相结合 Biomarker core)有可能极大地提高我们对疾病发病机制的理解， 因此提供了一定程度的精确度，以锚定临床和生物异质性通常观察到 痴呆症。此外，神经病理学在未来的干预中发挥着核心作用，就像尸检一样。 建立生物标记物的金标准适用性和实验干预的有效性。因此，我们 设想全国人大将继续在多个组成部分的研究项目中发挥中心作用，努力找到 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 进行多学科研究，同时提升核心诊断能力，以使能够检测到 不同的脑损伤途径使用新的方法。

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.