Core D: University of Kentucky Alzheimer's Disease Core Center

项目摘要/摘要：神经病理学核心 英国-ADRC神经病理学核心的总体目标是支持对正常大脑的研究 衰老、症状前AD、MCI、早、晚期AD、混合性痴呆综合征和其他痴呆 精神错乱。身体解剖将由我们的快速尸检小组对来自我们的 临床核心。我们将进行短时间的尸检，并将保持较高的尸检率。 这一核心是为帮助解决重要的研究问题而优化定制的。核心将提供脑组织， 供英国、其他ADRC和外部调查人员使用的脑脊液和其他生物检疫剂。核心意志 还提供共识会议确定的诊断、神经原纤维缠绕的量化、神经炎 8个脑区的斑块、弥漫性斑块、抗体定量、Braak分期、CERAD和NIA-Reagan 对所有尸检病例进行分期，同时评估α-突触核蛋白和TDP-43蛋白病变。 这个脑库已经连续运作了三十多年，有很好的记录，所以特别 应注意确保诊断的精益性、一致性和连续性。核心将维持一种组织 保存上述标本和活体患者的冰冻血清、血浆、棕黄色大衣和脑脊液。特价 重点将放在从数字病理学中生成严格的定量病理指标，以及 向调查人员提供认知完好的对照受试者的样本，没有抗体沉积和 稀疏的tau病理(成功的脑老化)和许多混合病理的病例。提供这些服务 样本将有助于临床-病理相关性研究和尖端研究，包括 赞助与AD基因组学、氧化应激、海马硬化/迟发性痴呆、路易痴呆相关的研究 身体、唐氏综合症和神经炎。将经常举行协商一致会议，与 帮助定义临床病理诊断的临床、生物标记、数据管理和统计核心 所有的尸检对象。神经病理核心与英国-ADRC的其他核心紧密结合， 并利用独特的机会进行纵向随访的临床与病理相关研究 研究对象。通过这些方法，我们将更好地了解正常的大脑衰老和向多细胞 痴呆症的病因学，目的是促进治疗或预防措施。神经病理学 CORE补充了UK-ADRC的其他核心，提供极其必要的诊断和组织 肯塔基大学和其他地方的许多尖端研究人员所需的样本。我们 将使用与脑部尸检、神经病理学相关的创新工具，建立在我们卓越的记录基础上 诊断、组织库和临床-病理相关性。我们的具体目标是： 目标1：提供最先进的神经病理和生物谱系资料库服务 目标2：利用神经病理学资源和专业知识为研究工作做出贡献 目标3：与其他核心整合，为行政、研究和教育任务作出贡献

Project Summary/Abstract: Neuropathology Core The overall objective of the Neuropathology Core of the UK-ADRC is to support research on normal brain aging, presymptomatic AD, MCI, early and late AD, mixed dementia syndromes, and other dementing disorders. Autopsies will be performed by our Rapid Autopsy Team on longitudinally followed subjects from our Clinical Core. We will perform short post-mortem interval autopsies, and we will maintain a high autopsy rate. This Core is optimally tailored to help address important research questions. The Core will provide brain tissue, CSF and other biospecimens for investigators at UK, other ADRCs, and outside investigators. The Core will also provide consensus conference determined diagnoses, quantitation of neurofibrillary tangles, neuritic plaques, and diffuse plaques from 8 brain regions, Ab quantitation, Braak staging, CERAD, and NIA-Reagan Institute staging on all autopsied cases, along with evaluation of alpha-synuclein and TDP-43 proteinopathy. This brain bank has been operating continuously for over three decades with a strong track record, so special care will be taken to ensure diagnostic excellence, consistency, and continuity. The Core will maintain a tissue bank of the above specimens and frozen serum, plasma, buffy coats and CSF from living patients. Special emphasis will be placed on generating rigorous quantititative pathologic metrics from digital pathology, and providing investigators with specimens from cognitively intact control subjects with no Ab deposition and sparse tau pathology (successful cerebral aging) and many cases with mixed pathologies. Providing these samples will contribute to clinical-pathological correlation studies and cutting-edge research that include sponsored studies related to AD genomics, oxidative stress, hippocampal sclerosis/LATE, dementia with Lewy bodies, Down syndrome, and neuroinflammation. Frequent consensus conferences will be held with the Clinical, Biomarker, and Data Management and Statistics Cores to help define clinical-pathological diagnoses on all autopsied subjects. The Neuropathology Core is strongly integrated with other Cores of the UK-ADRC, and exploits unique opportunities to conduct clinical-pathological correlative studies on longitudinally followed subjects. Through these methods we will better understand normal brain aging and the transition to multi- etiology dementia with the goal of contributing to therapeutic or preventive measures. The Neuropathology Core complements the other Cores of the UK-ADRC to provide extremely essential diagnoses and tissue samples that are required for many cutting-edge researchers at the University of Kentucky and elsewhere. We will build on our track record of excellence using innovative tools related to brain autopsies, neuropathological diagnoses, tissue banking, and clinical-pathological correlation. Our specific aims are: Aim 1: Provide state-of-the-art neuropathological and biospecimen repository services Aim 2: Leverage neuropathology resources and expertise to contribute to research efforts Aim 3: Integrate with other cores to contribute to administrative, research and educational missions