Neuropathology Core

摘要-耶鲁ADRC神经病理学核心 大脑的神经病理评估为疾病导向研究提供了重要的资源和资产。 通过将临床、基于生物标记物、遗传和神经影像的观察与病原学联系起来的神经科学 基于组织的变化。阿尔茨海默病(AD)的研究通过深入的神经病理学研究而得到加强 发现与其他明确的神经退行性疾病和/或 脑血管疾病和海马区硬化症等并存疾病。准确的尸检结果是 因此，对于验证候选生前生物标志物和成像特征至关重要。耶鲁大学ADRC 神经病理学核心旨在加强耶鲁大学ADRC的研究，并促进组织- 基于整个神经退行性疾病研究社区的阿尔茨海默病研究。这个 AD大脑的生物库将由平行收集的皮肤或硬脑膜来源的成纤维细胞补充 死亡个体，将被重新编程为诱导的多能干细胞(IPSC)。这种方法导致了 唯一配对的样本，允许对神经退行性疾病过程进行定向研究 冷冻/固定大脑样本，同时还提供同一个体的细胞培养模型。更重要的是，耶鲁是他的家 由于几十年来非人类灵长类(NHP)神经科学的卓越地位，导致了一个庞大的古老恒河猴群体。这个 将NHP脑纳入猕猴年龄相关神经退行性变的评估将允许 跨物种AD病理和成像的相关性，它将为高质量的 由于超微结构的良好控制，最小的尸检时间。神经病理学的核心 还将与耶鲁ADRC的其他核心密切互动。 这个应用程序的总体目标是开发和建立一个高度现代的生物库，它合并了 干细胞技术的进步与阿尔茨海默病分析的传统生物库方法 此外，它还提供了经过充分研究的NHP老化脑组织。圆满完成这些目标 将对耶鲁ADRC的整体成功产生重大影响。

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.