Neuropathology Core

神经病理学核心

• 批准号: 8909212
• 负责人: DENNIS WILLIAM DICKSON
• 金额: $ 16.06万
• 依托单位: MAYO CLINIC JACKSONVILLE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8909212
• 关键词: Alzheimer' s Disease; Antibodies; Area; Autopsy; Basal Ganglia; Binding; Biochemical; Biochemistry; Biological; Brain; Clinic; Clinical Research; Collection; Crystallins; Cytoplasmic Inclusion; DNA; Degenerative Disorder; Dentate nucleus; Diagnosis; Diagnostic; Disease; Electrons; Evaluation; Family; Family history of; Freezing; Gene Expression; Genes; Genetic; Goals; Gold; Harvest; Hippocampus (Brain); Histologic; Histology; Human; Immunohistochemistry; Institution; Instruction; Lead; Lesion; Lewy Bodies; Life; Microscopic; Microscopy; Midbrain structure; Molecular Biology; Motor; Neocortex; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurons; Parkinson Disease; Parkinsonian Disorders; Participant; Pathologic; Pathology; Patients; Pharmaceutical Preparations; Phenotype; Physicians; Play; Pontine structure; Principal Investigator; Process; Progressive Supranuclear Palsy; Qualifying; Recording of previous events; Research; Research Design; Research Personnel; Research Project Grants; Role; Sampling; Senile Plaques; Services; Staging; Structure of subthalamic nucleus; Substantia nigra structure; Syndrome; Tauopathies; Thalamic structure; Thioflavin S; Tissues; Translational Research; Ubiquitin; accurate diagnosis; alpha synuclein; basal forebrain; base; clinical practice; data collection evaluation; density; diagnosis standard; diagnostic accuracy; dopaminergic neuron; drug efficacy; endophenotype; gene discovery; genetic association; genetic variant; immunocytochemistry; in vivo; kindred; medical specialties; mouse model; neurofilament; neuropathology; novel; proband; protein TDP-43; synucleinopathy; tau Proteins; tau aggregation; tissue processing

The goals of Core D (Neuropathology) are to perform postmortem neuropathologic evaluations of participants in the Udall Center. In addition, Core D will provide neuropathologic support to research projects, in particular tau biochemical support and immunohistochemistry for Project 2 , as well as tissue processing and histology for Project 3. Core D will also assist Project 3 with electron microscopic studies. To accomplish these objectives, the specific aims of Core D will: Specific Aim 1. Perform standardized diagnostic neuropathologic evaluations and data collection on all brains harvested locally or sent to the Udall Center by referring physicians, with particular focus on cases followed by Core B. This will include a) immunostaining of cortical, hippocampal and basal forebrain sections for a-synuclein to record density of Lewy bodies in multiple cortical regions; b) characterizing non-Lewy body Parkinsonian degenerative disorders with immunocytochemistry, including antibodies to tau, TDP-43, ubiquitin, FUS, a-internexin and aB-crystallin, recording estimates of neuronal and glial lesions in neocortex, hippocampus, basal ganglia, thalamus, subthalamic nucleus, midbrain, pons, medulla and cerebellar dentate nucleus for cases with tauopathy; c) assessing Alzheimer type pathology with counts of senile plaques and neurofibrillary tangles in multiple cortical and subcortical areas with thioflavin-S fluorescent microscopy, and assign a Braak neurofibrillary tangle stage on all cases; and d) using validated neuropathologic research criteria for those disorders for which such criteria have been established and "best clinical practice" for uncommon disorders for which research criteria do not yet exist. Specific Aim 2. Provide frozen human brain samples or DNA to investigators in the Udall Center, particulady Projects 1 and 2, as well as to qualified investigators at other research institutions. Specific Aim 3. Assist Projects 2 with biochemical studies of tau protein in human brain samples. Specific Aim 4. Assist Project 3 with neuropathologic characterization of mouse models subjected to drug treatments and with electron microscopic support to evaluate effects of drugs on tau and a-synuclein fibrillization. RELEVANCE (See instructions): The "gold standard" for diagnosis of neurodegenerative disorders, such as Parkinson disease (PD), is neuropathology, which is the medical specialty that uses microscopic evaluation of tissue changes to arrive at a diagnosis. Accurate diagnosis is critical to finding genes and other factors that cause PD, which are the first steps in the process of finding a cure for PD and related disorders.

核心D（神经病理学）的目标是执行事后神经病理学评估 Udall中心的参与者。此外，核心D将为研究项目提供神经病理学支持， 特别是TAU生化支持和项目2的免疫组织化学以及组织加工 和项目3。CoreD的组织学还将帮助项目3进行电子显微镜研究。完成 这些目标，核心D的具体目标将： 特定目标1。对所有人进行标准化的诊断神经病理学评估和数据收集 大脑在本地收获或通过转诊医生发送到Udall中心，特别关注案件 其次是核心B 为了使A-突触核蛋白记录多个皮质区域的Lewy体密度； b）表征非腿部身体 具有免疫细胞化学的帕金森氏症退化性疾病，包括抗Tau的抗体，TDP-43， 泛素，FUS，A-Internexin和AB-晶状体，记录新皮层中神经元和神经胶质病变的估计值， 海马，基底神经节，丘脑，丘脑核核，中脑，脑海，脑，髓质和小脑齿​​状齿状 患有tauopathy病例的细胞核； c）用老年斑块和 具有硫非类荧光显微镜的多个皮质和皮质下区域的神经原纤维缠结，以及 在所有情况下，分配一个Braak神经原纤维缠结阶段； d）使用经过验证的神经病理学研究 建立此类标准的那些疾病的标准，以及“最佳临床实践” 研究标准尚不存在的罕见疾病。 特定目标2。向Udall Center的研究者提供冷冻的人脑样品或DNA， 特别是项目1和2的项目，以及其他研究机构的合格研究人员。 特定目的3。协助项目2在人脑样品中对tau蛋白的生化研究。 特定目的4。辅助项目3的神经病理表征，对受到药物的小鼠模型 治疗和电子显微镜支持，以评估药物对TAU和A-核蛋白的影响 纤维化。 相关性（请参阅说明）： 用于诊断神经退行性疾病的“金标准”，例如帕金森病（PD） 神经病理学，这是使用微观评估组织变化的医学专业 诊断。准确的诊断对于查找引起PD的基因和其他因素至关重要，这是 在寻找治疗PD和相关疾病的过程中的第一步。