Neuropath Core

1997年，FHS开始了大脑捐赠计划，目前有568名受试者和241名受试者 来验尸吧。作为一个社区老龄化的脑库，存在着一系列的病理现象，包括 大量参与者在死亡时认知完好无损(例如，CDR 0；32%)，轻度 认知障碍(19%)或精神错乱(48%)，其中34.2%可能患有或可能患有AD。这一光谱 疾病允许研究临床结果的不同病理。传统病理方法 用来表征淀粉样蛋白和tau蛋白在整个大脑中的分布是半定量的， AD的诊断依赖于达到指定的密度和区域受累阈值。 将血管疾病的神经病理特征转化为标准的量化方法仍不统一 以及对其他病理(例如，路易小体、海马硬化、嗜银颗粒病、 等)依赖于对区域密度的估计和对总体分布模式的总结印象。准确 由于混合病理的流行，病理负担的评估进一步复杂化， 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削弱 传统的半定量方法，并提供了显著增强的测量水平 准确性和客观性。拟议的神经病理核心建议继续神经病理 纵向应用半定量结合尸检的FHS参与者的特征 方法利用新技术对AD和脑血管病理进行精确量化。目标 神经病理学的核心是(1)执行最先进的诊断神经病理学，(2)开发新的 组织的定性和定量组织病理学特征的方法，(3)最佳储存和 分发脑组织，以及(4)为项目3和两个项目的其他辅助研究提供神经病理数据 弗雷明翰心脏研究-脑老化计划(FHS-BAP)和外部调查人员。FHS神经病理学 协议已经与波士顿大学阿尔茨海默病中心(BU ADC)在生物光谱方面保持一致 收集、阻止、染色和存储，并将通过一个 新资助的U54由神经病理学核心负责人Ann McKee和联合负责人托尔·斯坦领导。此外，a 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 向公众开放。

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.