Neuropathology and Biochemistry Core

神经病理学和生物化学核心

基本信息

批准号：
10022181
负责人：
DENNIS WILLIAM DICKSON
金额：
$ 39.26万
依托单位：
MAYO CLINIC JACKSONVILLE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-20 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10022181
关键词：
Aliquot Alzheimer&apos s disease related dementia American Amyloid Amyloid beta-42 Amyloid beta-Protein Area Autopsy Biochemistry Brain Brain region Cerebellum Clinic Clinical Clinical Research Collaborations Consensus Correlative Study Cryoelectron Microscopy DNA Data Data Collection Dementia Deposition Diagnostic Diagnostics Research Disease Education and Outreach Educational Activities Evaluation Experimental Designs Freezing Frequencies Genetic Goals Histologic Histology Human Image Analysis Immunohistochemistry Individual Institution Lesion Lewy Bodies Lewy Body Dementia Lewy neurites Liquid substance Measures Methods Microscopy Molecular Neurofibrillary Tangles Nitrogen Online Systems Paraffin Parkinson Disease Parkinson&apos s Dementia Parkinsonian Disorders Pathologic Pathology Patients Persons Powder dose form Preparation Process Proteins Proteomics Recommendation Reporting Research Research Personnel Research Project Grants Resolution Resources Sampling Scientist Senile Plaques Solubility Standardization Structure Substantia nigra structure Superior temporal gyrus Tauopathies Thioflavin S Tissue Sample Tissues Translational Research Tyrosine 3-Monooxygenase United States National Institutes of Health alpha synuclein base brain tissue case control clinical subtypes data sharing digital digital pathology endophenotype genetic analysis genetic information instrument mechanical force microscopic imaging neuron loss neuropathology patient outreach protein TDP-43 protein profiling putamen relational database research study statistics tau Proteins tau aggregation tau-1 tissue processing trait transcriptomics

项目摘要

PROJECT SUMMARY – NEUROPATHOLOGY AND BIOCHEMISTRY CORE Neuropathologic evaluation remains an important part of clinical and translational research on dementia with Lewy bodies (DLB) and Parkinsonian disease dementia (PDD), disorders that have been grouped in the research recommendations of NIH-sponsored Alzheimer Disease and Related Dementias (ADRD) recommendations as the Lewy body dementias (LBD). The purpose of the Core B: Neuropathology is to perform quantitative postmortem neuropathologic evaluations and data collection for all LBD brains that will be distributed to the CWOW scientists. The Core B will provide pulverized frozen human brain samples, brain homogenates, purified protein preparations (Aβ and α-Syn) or paraffin sections of LBD cases and matched controls to all CWOW investigators, as well as to qualified investigators at other research institutions as approved by the Executive Committee of Core A and the Mayo Clinic Biospecimen Committee. The quantitative traits generated include counts of cortical Lewy bodies, semiquantitative estimates of substantia nigra neuronal loss, dopaminergic deficiency in putamen with tyrosine hydroxylase immunohistochemistry and counts of senile plaques and neurofibrillary tangles in cortical and subcortical areas with thioflavin S fluorescent microscopy. Core B will perform digital microscopy and image analysis on sections processed for immunohistochemistry for α-Syn, phospho-tau and Aβ40, Aβ42, as additional other quantitative endophenotypes, such as phospho-TDP-43.

项目摘要 – 神经病理学和生物化学核心神经病理学评估仍然是痴呆症临床和转化研究的重要组成部分路易体 (DLB) 和帕金森病痴呆 (PDD)，这些疾病已归为 NIH 资助的阿尔茨海默病和相关痴呆症 (ADRD) 的研究建议建议作为路易体痴呆 (LBD) 核心 B：神经病理学的目的是对所有 LBD 大脑进行定量死后神经病理学评估和数据收集分发给CWOW科学家的Core B将提供粉碎的冷冻人脑样本，即大脑。 LBD 病例的匀浆、纯化蛋白制剂（Aβ 和 α-Syn）或石蜡切片以及匹配的对所有 CWOW 研究人员以及其他研究机构的合格研究人员进行控制经核心 A 执行委员会和梅奥诊所生物样本委员会批准。生成的数量性状包括皮质路易体的计数、实质的半定量估计黑质神经元损失、壳核多巴胺能缺乏（酪氨酸羟化酶免疫组织化学检测）和用硫黄素 S 计数皮质和皮质下区域的老年斑和神经原纤维缠结荧光显微镜检查核心 B 将对经过处理的切片进行数字显微镜检查和图像分析。免疫组织化学检测 α-Syn、磷酸化 tau 和 Aβ40、Aβ42，作为附加定量内表型，例如磷酸-TDP-43。