Neuropathology Core

神经病理学核心

• 批准号: 10431899
• 负责人: Anita Juliane Huttner
• 金额: $ 33.1万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10431899
• 关键词: Aging; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease pathology; Autopsy; B-Lymphocytes; Biological Markers; Biopsy Specimen; Brain; Cell Culture Techniques; Cell Line; Cerebrovascular Disorders; Characteristics; Clinical; Collaborations; Collection; Communities; Data; Data Analyses; Data Collection; Diagnosis; Disease; Dura Mater; Fibroblasts; Freezing; Genetic; Goals; Hippocampus (Brain); Home; Human; Image; Individual; Investigation; Lewy Body Disease; Link; Macaca mulatta; Medical Genetics; Methodology; Modeling; NIH Program Announcements; Nerve Degeneration; Neurodegenerative Disorders; Neurosciences; Participant; Pathogenicity; Pathologic; Patients; Process; Research; Research Personnel; Resolution; Resources; Rhesus; Sampling; Skin; Spinal Cord; Time; Tissue Sample; Tissues; Vascular Diseases; Work; age related neurodegeneration; aged; base; biobank; brain tissue; cell bank; cerebrovascular; clinical biomarkers; comorbidity; data management; data standards; demented; design; hippocampal sclerosis; imaging biomarker; induced pluripotent stem cell; mind control; neuroimaging; neuropathology; nonhuman primate; novel; pathology imaging; statistics; stem cell technology; success

SUMMARY – Yale ADRC Neuropathology Core The neuropathological assessment of brains provides a critical resource and asset for disease-oriented neuroscience by connecting clinical, biomarker-based, genetic and neuroimaging observations to pathogenic tissue-based changes. Alzheimer’s Disease (AD) research was enhanced by thorough neuropathological studies uncovering closely inter-related histopathological features with other defined neurodegenerative diseases and/or co-morbidities such as cerebrovascular disease and hippocampal sclerosis. Precise postmortem diagnosis is therefore critical for validating candidate antemortem biomarkers and imaging characteristics. The Yale ADRC Neuropathology Core has been designed to enhance research within the Yale ADRC and to promote tissue- based Alzheimer Disease research throughout the neurodegenerative disease research community. The biobanking of AD brains will be supplemented by the parallel collection of skin or dura derived fibroblasts from deceased individuals, which will be reprogrammed to induced pluripotent stem cells (IPSC). This approach leads to uniquely paired samples that allow the directed investigation of neurodegenerative disease processes in frozen/fixed brain samples while also providing a cell culture model of the same individual. Further, Yale is home to a large aged rhesus colony due to decades of pre-eminence of non-human primate (NHP) neuroscience. The incorporation of NHP brains the for assessment of age-related neurodegeneration in rhesus macaque will allow correlation of AD pathology and imaging across species, and it will provide high quality tissue samples for high resolution ultrastructure due to due to a well-controlled, minimal postmortem interval. The Neuropathology Core will also closely interact with other Cores of the Yale ADRC. The overarching goal of this application is to develop and establish a highly contemporary biobank, which merges traditional biobanking approaches with advancements in stem cell technology for the analysis of Alzheimer’s Disease, and also offers access to well-studied aged NHP brain tissue. Successful completion of these goals will have a major impact on the overall success of the Yale ADRC.

总结-耶鲁ADRC神经病理学核心 大脑的神经病理学评估为疾病导向的 通过将临床、基于生物标志物的、遗传和神经影像学观察与致病性 基于组织的变化。阿尔茨海默病（AD）的研究得到了全面的神经病理学研究的加强 发现与其他定义的神经退行性疾病密切相关的组织病理学特征和/或 合并症如脑血管疾病和海马硬化。精确的尸检诊断 因此对于验证候选的死前生物标志物和成像特征至关重要。耶鲁ADRC 神经病理学核心旨在加强耶鲁ADRC内的研究，并促进组织- 在整个神经退行性疾病研究界的阿尔茨海默病研究。的 AD脑的生物库将通过平行收集皮肤或硬脑膜来源的成纤维细胞来补充， 死亡的个体，将被重新编程为诱导多能干细胞（IPSC）。这种方法导致 唯一配对的样本，允许直接调查神经退行性疾病的过程， 冷冻/固定的脑样品，同时还提供同一个体的细胞培养模型。此外，耶鲁是 由于非人类灵长类动物（NHP）神经科学数十年的卓越地位，的 将NHP脑掺入恒河猴中用于评估年龄相关的神经变性将允许 AD病理学和跨物种成像的相关性，并且它将为高风险患者提供高质量的组织样本。 由于控制良好，死后时间最短，因此超微结构分辨率较低。神经病理学核心 还将与耶鲁ADRC的其他核心密切互动。 该应用程序的首要目标是开发和建立一个高度现代化的生物库， 传统的生物库方法与干细胞技术的进步，用于分析阿尔茨海默氏症 疾病，并提供了获得充分研究的老年NHP脑组织。圆满完成这些目标 将对耶鲁ADRC的整体成功产生重大影响。