Neuropath Core

神经病核心

• 批准号: 8882843
• 负责人: JUAN TRONCOSO
• 金额: $ 28.35万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8882843
• 关键词: Accounting; Age; Age-Years; Antibodies; Autopsy; Basic Science; Biochemical; Biological Markers; Brain; Brain Stem; Cataloging; Catalogs; Clinical; Clinical Research; Collaborations; Collection; Complement; Controlled Study; Corpus striatum structure; Databases; Diagnosis; Disease; Doctor of Philosophy; Etiology; Evaluation; Event; Gene Mutation; Genetic; Genetically Engineered Mouse; Genomics; Goals; Histologic; Human; Institutes; Laboratories; Lesion; Lewy Body Dementia; Lewy Body Disease; Methodology; Methods; Minority; Molecular; Molecular Genetics; Molecular Probes; Morbidity - disease rate; Mus; Mutation; National Institute of Neurological Disorders and Stroke; Nerve Degeneration; Neurons; Parkinson Disease; Pathogenesis; Pathologic; Pathology; Patients; Phenotype; Population; Preparation; Proteomics; Recommendation; Research; Research Personnel; Research Project Grants; Resources; SNP genotyping; Source; Specimen; Staging; Structure; Substantia nigra structure; Surveys; TNFRSF5 gene; Techniques; Technology; Tissue Banks; Tissues; Universities; alpha synuclein; brain tissue; case control; clinical Diagnosis; developmental disease; disorder control; disorder risk; exome sequencing; experience; genetic profiling; genome sequencing; genome-wide; improved; insight; mouse model; neurogenetics; neuroimaging; neuropathology; novel; olfactory bulb; pre-clinical; programs; research study

CORE SUMMARY Neuropathology Core C The Neuropathology Core (Core C) of the Johns Hopkins Udall Parkinson's Disease Research Center has three overarching goals. The first is to conduct postmortem neuropathological assessments in subjects from the Clinical Core and to distribute autopsy brain tissues for research to Projects 1, 2 & 4 and the Proteomic Core. The second is to obtain a comprehensive genetic profile of all the postmortem tissues available in the Udall Center collection. The third is to provide support for the morphological evaluation of genetically engineered mouse models by investigators in Projects 1, 2 & 4. The specific aims of Core C are as follows: (1) to arrange and perform neuropathological autopsies of cases of Parkinson's disease (PD) and Lewy body disease (LBD), and control subjects followed by the Clinical Core, and to formulate pathological diagnoses; (2) to accession, prepare, catalog, and assist in the analysis of human postmortem tissues from cases of PD/LBD and related disorders, as well as age-matched and also younger controls for studies proposed in Projects 1, 2 & 4 and the Proteomic Core; (3) to characterize the molecular genetic profiles of PD/LBD postmortem tissues available in the BRC through a collaboration with the Laboratory of Neurogenetics at NIA (A. Singleton, Ph.D.); and (4) to use CLARITY technology for preparation of mouse brain tissues in support of studies delineated in Projects 1, 2 & 4. Despite recent advances in neuroimaging postmortem brain examination remains indispensable. For accurate diagnosis of PD (Parkinson's disease) and LBD (Lewy body disease) in our experience, ~20% of cases clinically diagnosed as PD have other etiologies, and >30% of the cases have coexisting morbidities. Moreover, since autopsies are the essential source of tissues for studying molecular/biochemical abnormalities of the human brain associated with PD/LBD, a thorough pathological characterization is important before tissues can be used in studies proposed in Projects 1, 2 & 4 and by the Proteomic Core. Core C is expanding its postmortem tissue collection to include a large number of specimens from younger subjects (16 to 65 years) suitable to examine the very early stages of PD/LBD pathology and its pathogenesis. These tissues are accessioned through collaboration with the Lieber Institute for Developmental Disorders at Johns Hopkins. Finally, by using CLARITY, a state-of-the-art morphological technique implemented by Core C, investigators in Projects 1, 2 & 4 will be able to produce translucent preparations of whole mouse brains that allow interrogation of molecular events not only of single neuronal populations but of networks relevant to PD and LBD.

核心摘要 神经病理学核心C 约翰霍普金斯大学尤德尔帕金森氏病研究中心的神经病理学核心(C核心) 三个首要目标。第一个是对受试者进行死后神经病理学评估 临床核心和将尸检脑组织分配到项目1、2和4以及蛋白质组研究 核心。第二种方法是获得所有死后组织的全面基因图谱。 Udall Center收藏。三是为遗传性状的形态评价提供支持 由研究人员在项目1、2和4中设计的老鼠模型。核心C的具体目标如下： (1)安排和进行帕金森病(PD)和路易小体的神经病理尸检 疾病(LBD)、对照受试者遵循临床核心，并制定病理诊断； (2)加入、准备、编目和协助分析人类死后组织 PD/LBD和相关疾病，以及年龄匹配的和年轻的对照研究 项目1、2、4与蛋白质组核心；(3)研究PD/LBD的分子遗传学特征 通过与NIA神经遗传学实验室的合作，在BRC中获得死亡组织 (A.Singleton，Ph.D.)；及(4)使用Clarity技术制备小鼠脑组织，以支持 项目1、2和4中描述的研究。 尽管最近在神经成像方面取得了进展，但尸检仍然是必不可少的。为准确起见 帕金森氏病(PD)和路易体病(LBD)的诊断在我们的经验中，约20%的病例 临床诊断为帕金森病有其他病因，30%的病例并存疾病。 此外，由于身体解剖是研究分子/生化异常的基本组织来源 对于与PD/LBD相关的人脑，彻底的病理特征在 组织可用于项目1、2和4以及蛋白质组核心提出的研究。核心C正在扩张 其死后组织收集包括大量年轻受试者(16至65岁)的标本 适用于研究PD/LBD病理及其发病机制的非常早期阶段。这些组织是 通过与约翰·霍普金斯大学利伯发育障碍研究所的合作获得。 最后，通过使用由Core C实现的最先进的形态技术Clarity，研究人员在 项目1、2和4将能够生产全鼠大脑的半透明制剂，从而使 不仅询问单个神经元群体的分子事件，而且询问与PD和Pd相关的网络的分子事件 LBD。