Core C: Neuropathology

核心 C：神经病理学

• 批准号: 8754970
• 负责人: DENNIS WILLIAM DICKSON
• 金额: $ 19.61万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8754970
• 关键词: Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Animal Model; Animals; Antibodies; Autopsy; Basic Science; Biological Markers; Brain; C9ORF72; Clinic; Clinical; Clinical Research; Computerized Medical Record; Corticospinal Tracts; Degenerative Disorder; Diagnostic; Disease; Early Diagnosis; Enrollment; Evaluation; Evaluation Reports; Family; Feedback; Fixatives; Freezing; Frontotemporal Lobar Degenerations; Genes; Genetic; Goals; Harvest; Histologic; Histology; Human; Immunohistochemistry; Institution; Investigation; Letters; Link; Luxol Fast Blue MBS; Medical Education; Methods; Monitor; Mus; Mutation; Nerve Degeneration; Neurodegenerative Disorders; Organ; Outcome; PGRN gene; Paraffin; Pathogenesis; Pathologist; Pathology; Patients; Peripheral Nerves; Persons; Physicians; Play; Process; Protocols documentation; Qualifying; Quality Control; RNA-Binding Proteins; Relative (related person); Research; Research Personnel; Role; Sampling; Skeletal Muscle; Specimen; Specimen Handling; Spinal Cord; Staining method; Stains; Syndrome; Tissue Embedding; Tissue Sample; Tissues; Ubiquitin; Validation; Work; neuropathology; programs; protein TDP-43; research study; sarcoma; superoxide dismutase 1; tissue processing

PROJECT SUMMARY/ABSTRACT The discovery of mutations in C9ORF72 as a cause of both FTLD and ALS provides a clear link between these two degenerative diseases and suggests that they form a clinicopathologic disease spectrum. Research on C9ORF72 related neurodegenerative disorders, thus, holds promise to unlock secrets related to this disease spectrum. Postmortem neuropathology plays an important role in establishing the range of pathology in both ALS and FTLD, as well as documenting other disease processes that may have contributed to the clinical syndrome. As animal models are developed to study disease pathogenesis of ALS and FTLD, neuropathologic studies are increasingly important to monitor outcomes of experimental manipulations and for comparison to human disorders. Core C participates in these activities as well as providing tissue samples to investigators obtain from postmortem studies. Core C will work closely with clinical coordinators to obtain rapid autopsies of patients enrolled in clinical studies in Core B. In addition to brain and spinal cord, tissue samples will also be obtained from skeletal muscle, peripheral nerve and the internal organs. Core C will bank these fixed and frozen tissue specimens and process them for histologic studies. Core C will provide diagnostic evaluations. Core C will provide tissue samples for genetic studies, basic research, and clinicopathologic studies in Projects 1, 2 and 3, respectively. Core C will provide technical support to Projects 2 and 3 with respect to neurohistology of human and animal brains. The specific aims of the core are as follows: Specific Aim 1. For enrolled subjects in the deeded autopsy program who die during the course of the project, conduct autopsies to harvest brain, spinal cord, skeletal muscle and peripheral nerve, as well as samples from internal organs, with a portion of each sample frozen for subsequent research and another portion preserved in fixative for diagnostic evaluation and for future research studies. A neuropathologic diagnostic evaluation will be performed on each case using a standardized protocol. Upon completion of the diagnostic evaluation, reports will be entered into the electronic medical record and copies will be sent to the next-of-kin along with an explanatory letter in lay person terms. Specific Aim 2. Process and assist in the neuropathologic characterization of mouse brains from Project 2, and assist with characterizing antibodies generated in Project 2. Specific Aim 3. Provide tissue samples to Projects 1, 2 and 3 as well as to qualified investigators at other institutions. Core C will facilitate research in the program project, but also contribute to medical education, physician quality control, and feedback to families whose relatives were engaged in research on ALS and FTLD.

项目摘要/摘要 C9orf72中突变是FTLD和ALS的原因提供了明确的链接 在这两种退化性疾病之间，并表明它们形成了临床病理疾病谱。 因此，对C9orf72相关神经退行性疾病的研究有望解锁与 这种疾病范围。验尸神经病理学在建立一系列范围中起着重要作用 ALS和FTLD的病理学，以及可能导致的其他疾病过程 到临床综合征。随着动物模型的发展来研究ALS和FTLD的疾病发病机理 神经病理学研究越来越重要，对于监测实验操作的结果和 与人类疾病进行比较。核心C参与这些活动，并提供组织样本 研究人员从死后研究中获得。核心C将与临床协调员紧密合作以获得快速 在核心B中入学的患者的尸检。除了大脑和脊髓外，组织样本还将 还可以从骨骼肌，周围神经和内部器官中获得。 C核心将把这些固定固定，并且 冷冻的组织标本并加工它们进行组织学研究。核心C将提供诊断评估。核 C将在项目1、2中提供组织样品，用于遗传研究，基础研究和临床病理研究 和3分别。 Core C将为项目2和3的技术支持提供有关神经组织学的技术支持 人类和动物的大脑。核心的具体目的如下：特定目标1。 在项目过程中死亡的契据尸检计划，进行尸检以收获大脑，脊柱 绳索，骨骼肌肉和周围神经，以及内部器官的样品，每个器官的一部分 样本冻结以进行后续研究，并保存在固定剂中的另一部分，用于诊断评估和 未来的研究。在每种情况下，都将使用 标准化协议。诊断评估完成后，将输入报告中的报告 病历和副本将以外行的方式发送到近亲。 具体目的2。过程和协助项目2的小鼠大脑的神经病理表征， 协助项目2中产生的抗体。特定目的3。向项目提供组织样本 1、2和3以及其他机构的合格调查员。核心C将促进该计划的研究 项目，但也有助于医学教育，医师质量控制以及向家庭的反馈 亲戚从事ALS和FTLD的研究。