Neuropath Core

神经病理学核心-项目摘要 神经病理学(NP)核心将提供独特的资源来支持维克森林阿尔茨海默氏症 疾病研究中心(ADRC)专注于从正常衰老到MCI、AD和相关疾病的过渡， 以及代谢和血管风险通路在这些转变中的作用。核心将促进创新 在与AD相关的所有领域进行研究。为了实现这些目标，核心将提供最先进的 脑和其他生物标本的收集、储存和分布，建立神经病理学诊断 死亡临床核心(CC)参与者，并为非人类灵长类(NHP)提供资源和专业知识 关键机制和治疗研究的模型。国家警察核心也将对亚洲复兴开发中心的主题作出贡献 通过一项独特的计划减少健康差距，重点是增加代表不足的人的脑捐赠 组(URG)。通过这些活动，NP核心将对许多国家做出有影响力的贡献 阿尔茨海默氏症项目法案(NAPA)研究里程碑，如支持深度、纵向分子 包括URGs(1A)、数据和样本共享(3A、4D)的队列的内部表型，以及发展 下一代动物模型(4A、B、C)。 NP Core目前维护着DNA、血液和脑脊液(CSF)的生物谱系储存库 来自亚洲发展研究中心及其附属研究的1100名性格良好的参与者。在接下来的周期中，我们 将继续存档来自ADRC CC参与者的生物标本，这些参与者接受了仔细的代谢和 血管特征。DNA、脑脊液和血液将提供给NCRAD、其他财团和个人 调查人员。AD-CSF生物标志物(Ab40、AB42、tau和p-tau181)在所有参与者身上都进行了严格的测量 接受腰椎穿刺术(LP)，血液和脑脊液生物标志物有专门的专业知识 代谢和血管疾病。我们不断评估在鉴定新的血液和脑脊液方面的科学进展 ADRD的生物标志物，并将随着该领域的发展而实施这些标记。此外，人类对大脑、血液的协议 和CSF收集已应用于NHP模型，创建了AD研究的独特资源 社区可以进行关键的翻译研究。在上一个周期中，我们演示了我们的NHP模型 是否有类似早期AD的神经病理改变，如淀粉样斑块、AD样脑脊液AB42谱、脑组织 新陈代谢不足，大脑体积减少。关于NHP和其他模型(啮齿类、有机类)的咨询将 有空。 总之，通过对具有良好特征的队列进行仔细的临床病理分析，独特的生物样本 资源库和新颖的翻译模型，NP核心将促进WF ADRC主题，并提供 研究潜在机制、新的生物标记物和治疗靶点的特殊资源 从正常老化到MCI和ADRD的影响进展。

Neuropathology Core – Project Summary The Neuropathology (NP) Core will provide unique resources to support the Wake Forest Alzheimer’s Disease Research Center (ADRC) focus on transitions from normal aging to MCI, AD, and related disorders, and the role of metabolic and vascular risk pathways in these transitions. The Core will foster innovative research in all areas relevant to AD. To accomplish these goals, the Core will provide state-of-the-art collection, storage, and distribution of brain and other biospecimens, establish neuropathological diagnoses of decedent Clinical Core (CC) participants, and provide resources and expertise for non-human primate (NHP) models for pivotal mechanistic and therapeutic research. The NP Core will also contribute to the ADRC theme of health disparities with a unique program focused on increasing brain donation from underrepresented groups (URGs). Through these activities, the NP Core will make impactful contributions to many National Alzheimer’s Project Act (NAPA) Research Milestones, such as supporting deep, longitudinal molecular endophenotyping of cohorts that include URGs (1A), data and sample sharing (3A, 4D), and development of the next generation of animal models (4A, B, C). The NP Core currently maintains a biospecimen repository of DNA, blood, and cerebrospinal fluid (CSF) from >1,100 well-characterized participants from the ADRC and its affiliated studies. In the coming cycle, we will continue to archive biospecimens from ADRC CC participants who have received careful metabolic and vascular characterization. DNA, CSF and blood will be provided to NCRAD, other consortia, and individual investigators. AD CSF biomarkers (Ab40, Ab42, tau, and p-tau181) are rigorously measured on all participants who undergo lumbar puncture (LP), and special expertise is available for blood and CSF biomarkers of metabolic and vascular disease. We continually assess scientific advances in identifying novel blood and CSF biomarkers of ADRD and will implement these as the field evolves. Further, human protocols for brain, blood and CSF collection have been applied to NHP models, creating a unique resource with which the AD research community can conduct pivotal translational research. In the past cycle, we demonstrated that our NHP model has neuropathologic changes similar to early AD such as amyloid plaques, AD-like CSF Ab42 profiles, cerebral hypometabolism, and reduced brain volumes. Consultation about NHP and other models (rodent, organoid) will be available. In summary, through careful clinico-pathologic analysis of well characterized cohorts, unique biospecimen repositories, and novel translational models, the NP Core will promote the WF ADRC themes, and provide an exceptional resource to investigate underlying mechanisms, novel biomarkers, and therapeutic targets that impact progression from normal aging to MCI and ADRD.