Neuropath Core

神经病核心

• 批准号: 10256772
• 负责人: Ann C. McKee
• 金额: $ 55.64万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10256772
• 关键词: Alzheimer' s Disease; Alzheimer' s disease pathology; Amyloid; Amyloid beta-Protein; Ancillary Study; Argyrophilic Grain Disease; Attenuated; Autopsy; Behavioral; Biochemical; Biological Assay; Biological Sciences; Boston; Brain; Cell Count; Cessation of life; Clinical; Cognitive; Collection; Communities; Consensus; Data; Dementia; Development; Diagnosis; Diagnostic; Digital Libraries; Disease; Elderly; Enrollment; Epitopes; Evaluation; Family member; Framingham Heart Study; Funding; Future; Genetic Markers; Gliosis; Heterogeneity; Image Analysis; Immunohistochemistry; Lewy Bodies; Magnetic Resonance Imaging; Measurement; Measures; Methods; Monitor; Myelin; Outcome; Participant; Pathologic; Pathology; Pattern; Phenotype; Prevalence; Proteins; Protocols documentation; Qualitative Methods; Recording of previous events; Research Personnel; Slide; Specific qualifier value; Stains; Systems Analysis; Technology; Time; Tissues; Translations; Universities; Vascular Diseases; aging brain; brain tissue; cerebrovascular pathology; clinical Diagnosis; cohort; cytokine; demented; density; digital; hippocampal sclerosis; impression; meetings; mild cognitive impairment; neuroinflammation; neuropathology; new technology; novel; operation; programs; tau Proteins

In 1997, the FHS began its brain donation program, and has 568 currently enrolled subjects and 241 who have come to autopsy. As a community-aging brain bank, there is a spectrum of pathologies present, including a significant number of participants that were cognitively intact at the time of death (e.g., CDR 0; 32%), mild cognitively impaired (19%), or demented (48%), including 34.2% with possible or probable AD. This spectrum of disease allows for the study of heterogeneous pathologies on clinical outcomes. Traditional pathological methods used to characterize the distribution of amyloid and tau throughout the brain are semi-quantitative and the diagnosis of AD is dependent on meeting specified thresholds of density and regional involvement. Neuropathological characterization of vascular disease into standard quantification methods is still not uniform and quantification of other pathologies (e.g., Lewy bodies, hippocampal sclerosis, argyrophilic grain disease, etc.) relies on estimation of regional density and a summary impression of overall distribution patterns. Accurate assessment of pathological burden is further complicated by the prevalence of mixed pathologies, which increases with advanced age. Digital technologies offer an exciting opportunity to attenuate the limitations of traditional semi-quantitative methods and provide a level of measurement that is significantly enhanced in its precision and objectivity. The proposed Neuropathology Core proposes to continue neuropathological characterization of FHS participants who come to autopsy integrating longitudinally applied semi-quantification methods with new technologies to allow precise quantification of AD and cerebrovascular pathologies. The aims of the Neuropathology Core are (1) perform state-of-the-art diagnostic neuropathology, (2) develop novel methods for qualitative and quantitative histopathological characterization of the tissue, (3) optimally store and distribute brain tissue, and (4) provide neuropathological data for Project 3 and other ancillary studies by both Framingham Heart Study-Brain Aging Program (FHS-BAP) and external investigators. FHS' neuropathological protocol is already aligned with the Boston University Alzheimer Disease Center (BU ADC) in biospecimen collection, blocking, staining and storage, and will be further aligned with 7 other brain bank cohorts through a newly funded U54 led by Neuropathology Core Leader, Ann McKee and co-Leader Thor Stein. In addition, a digital library of the pathology slides will be generated for each participant and through the Data Core, will be made publicly available.

1997年，FHS开始了脑部捐赠计划，目前有568名受试者入组，其中241名受试者已入组。 来尸检。作为一个社区老龄化脑库，存在一系列的病症，包括 大量参与者在死亡时认知完好（例如，CDR 0；32%）、轻度 认知障碍 (19%) 或痴呆 (48%)，其中 34.2% 可能患有 AD。这个谱 疾病允许研究异质病理学对临床结果的影响。传统病理方法 用于表征淀粉样蛋白和 tau 蛋白在整个大脑中的分布的特征是半定量的， AD 的诊断取决于是否满足指定的密度阈值和区域受累。 血管疾病的神经病理学表征转化为标准量化方法仍不统一 以及其他病理学的量化（例如路易体、海马硬化、嗜银颗粒病、 等）依赖于区域密度的估计和总体分布模式的总结印象。准确的 由于混合病理的普遍存在，病理负担的评估变得更加复杂， 随着年龄的增长而增加。数字技术提供了一个令人兴奋的机会来减少 传统的半定量方法，并提供了显着增强的测量水平 精确性和客观性。拟议的神经病理学核心提议继续神经病理学 结合纵向应用半量化进行尸检的 FHS 参与者的特征描述 采用新技术的方法可以精确量化 AD 和脑血管病理。目标 神经病理学核心包括 (1) 执行最先进的诊断神经病理学，(2) 开发新颖的 对组织进行定性和定量组织病理学表征的方法，(3) 最佳存储和 分发脑组织，(4) 为项目 3 和双方的其他辅助研究提供神经病理学数据 弗雷明汉心脏研究-大脑老化计划 (FHS-BAP) 和外部研究人员。 FHS的神经病理学 协议已在生物样本方面与波士顿大学阿尔茨海默病中心 (BU ADC) 保持一致 收集、封闭、染色和储存，并将通过 新资助的 U54 由神经病理学核心领导者 Ann McKee 和联合领导者 Thor Stein 领导。此外，还有一个 将为每个参与者生成病理幻灯片的数字图书馆，并通过数据核心，将 公开发布。