Neuropath Core

1997年，FHS开始了大脑捐赠计划，目前有568名参与者，241名参与者 来解剖。作为一个社区老龄化的大脑银行，存在一系列病理学，包括 大量在死亡时认知完整的参与者（例如，CDR 0; 32%），轻度 认知受损（19%）或痴呆（48%），包括34.2%可能或很可能AD。这种光谱 疾病允许研究异质性病理学对临床结果的影响。传统病理学方法 用于表征淀粉样蛋白和tau蛋白在整个大脑中的分布的方法是半定量的， AD的诊断依赖于满足密度和区域累及的特定阈值。 神经病理学表征血管疾病的标准量化方法仍不统一 以及其它病理的量化（例如，路易体海马硬化嗜银颗粒病 等等）。依赖于对区域密度的估计和对总体分布模式的概括印象。准确 病理负担的评估由于混合病理的流行而进一步复杂化， 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，以减轻 传统的半定量方法，并提供了一个测量水平，大大提高了其 精确和客观。拟议的神经病理学核心建议继续神经病理学 对前来尸检的FHS参与者进行纵向应用半定量的表征 采用新技术的方法可以精确量化AD和脑血管病变。目标 神经病理学的核心是（1）进行最先进的诊断神经病理学，（2）开发新的 用于组织的定性和定量组织病理学表征的方法，（3）最佳储存， 分发脑组织，以及（4）为项目3和其他辅助研究提供神经病理学数据， 心脏研究-脑老化计划（FHS-BAP）和外部研究者。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）在生物标本 收集、封闭、染色和储存，并将通过一项研究与其他7个脑库队列进一步对齐。 新资助的U54由神经病理学核心领导人Ann McKee和联合领导人Thor Stein领导。另外还有按 将为每位参与者生成病理学切片的数字库，并通过数据核心， 公开提供。

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.