Neuropath Core

神经病核心

• 批准号: 10262851
• 负责人: Thomas J Montine
• 金额: $ 37.48万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10262851
• 关键词: Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer’s disease biomarker; Animal Model; Area; Biological Markers; Biological Models; Biological Specimen Banks; Blood; Blood Vessels; Brain; Cerebrospinal Fluid; Cerebrum; Clinical; Collaborations; Collection; Communities; Consent; Consultations; DNA; DNA Repository; Data; Data Set; Development; Diagnosis; Diagnostic; Disease; Education; Enrollment; Evaluation; Fostering; Functional disorder; Goals; Human; Individual; Internet; Leadership; Liquid substance; Measurement; Measures; Mentors; Metabolic; Metabolic Diseases; Methods; Microscopy; Modeling; Molecular; Multi-Ethnic Study of Atherosclerosis; Neurodegenerative Disorders; Organoids; Participant; Pathologic; Pathology; Pathway interactions; Procedures; Protocols documentation; Research; Research Personnel; Resources; Risk; Rodent; Role; Sampling; Scientific Advances and Accomplishments; Senile Plaques; Specimen; Spinal Puncture; Technology; Therapeutic Human Experimentation; Therapeutic Studies; Translational Research; Underrepresented Populations; Universities; Vascular Diseases; Washington; biological specimen archives; brain volume; clinical center; cohort; data management; distributed data; education research; endophenotype; forest; health disparity; innovation; inter-institutional; neuropathology; next generation; nonhuman primate; normal aging; novel; novel marker; operation; programs; recruit; repository; sample collection; symposium; tau Proteins; therapeutic target; tissue biomarkers; translational model; vascular risk factor; virtual

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.

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病 疾病研究中心 (ADRC) 专注于从正常衰老到 MCI、AD 和相关疾病的转变， 以及代谢和血管风险途径在这些转变中的作用。核心将培育创新 与 AD 相关的所有领域的研究。为了实现这些目标，Core 将提供最先进的 收集、储存和分发大脑和其他生物样本，建立神经病理学诊断 已故临床核心 (CC) 参与者，并为非人类灵长类动物 (NHP) 提供资源和专业知识 关键机制和治疗研究的模型。 NP Core 也将为 ADRC 主题做出贡献 通过一项独特的计划来消除健康差异，该计划的重点是增加代表性不足的人的大脑捐赠 组（URG）。通过这些活动，NP 核心将为许多国家做出有影响力的贡献 阿尔茨海默病项目法案 (NAPA) 研究里程碑，例如支持深层、纵向分子研究 队列的内表型分析，包括 URG (1A)、数据和样本共享 (3A、4D)，以及开发 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) 的生物样本库 来自 ADRC 及其附属研究的超过 1,100 名特征鲜明的参与者。在接下来的周期中，我们 将继续存档 ADRC CC 参与者的生物样本，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。对所有参与者均严格测量 AD CSF 生物标志物（Ab40、Ab42、tau 和 p-tau181） 接受腰椎穿刺 (LP) 的患者，并且可以针对以下患者的血液和脑脊液生物标志物提供特殊专业知识 代谢和血管疾病。我们不断评估识别新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。此外，人类大脑、血液的协议 和 CSF 收集已应用于 NHP 模型，为 AD 研究创造了独特的资源 社区可以进行关键的转化研究。在过去的周期中，我们证明了我们的 NHP 模型 具有与早期 AD 类似的神经病理学变化，如淀粉样斑块、AD 样脑脊液 Ab42 谱、脑 新陈代谢减退，脑容量减少。关于 NHP 和其他模型（啮齿动物、类器官）的咨询将 可用。 总之，通过对特征明确的队列进行仔细的临床病理分析，独特的生物样本 存储库和新颖的翻译模型，NP Core 将推广 WF ADRC 主题，并提供 研究潜在机制、新型生物标志物和治疗靶点的特殊资源 影响从正常衰老到 MCI 和 ADRD 的进展。