The Vervet Research Colony as Biomedical Resource

作为生物医学资源的黑长尾黑长尾猴研究群体

• 批准号: 10710813
• 负责人: Matthew Jorgensen
• 金额: $ 32.85万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10710813
• 关键词: African Green Monkey; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer’s disease biomarker; Amyloid beta-42; Animals; Behavior; Behavioral; Biological Markers; Blood; Blood specimen; Brain; Brain region; Cercopithecus tantalus; Cerebrum; Characteristics; Computer software; Data; Dementia; Development; Disease; Foundations; Functional disorder; Future; Gait speed; Glucose; Goals; Health; Hippocampus; Home; Home environment; Human; Impairment; Individual; Intervention Studies; LAMC2 gene; Light; Liquid substance; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Memory; Metabolic; Methodology; Modeling; Monitor; Motor Activity; Movement; Nerve Degeneration; Pattern; Phase; Plasma; Positioning Attribute; Positron-Emission Tomography; Preventive measure; Primates; Research; Resources; Sedation procedure; Short-Term Memory; Signal Transduction; Space Perception; Speed; Structure; System; TREM2 gene; Technology; Time; age effect; age related; aged; aging brain; amnestic mild cognitive impairment; amyloid pathology; behavior measurement; biomedical resource; cognitive testing; fluorodeoxyglucose positron emission tomography; forest; frontal lobe; glucose metabolism; mental state; metabolic rate; neurofilament; neuropathology; sensor; social group; tau-1; vervet

PROJECT SUMMARY Vervet monkeys (Chlorocebus aethiops sabaeus) develop age-related amyloid pathology that resembles very early stages of Alzheimer's disease in humans. Hippocampal hypometabolism and volume reduction occur in amnestic mild cognitive impairment in humans, a condition characterized by impaired everyday memory which often precedes development of Alzheimer's disease, but the effect of age on hippocampal function in vervets is not known. Determining how age and Alzheimer's-related biomarkers are associated with hippocampal structure and function in vervets would dramatically enhance the utility of this species as a model for age- related cognitive impairments and early-stage Alzheimer's disease. As a first, exploratory step towards characterizing hippocampal structure and function in aging vervets, the goal of this application is to develop a continuous tracking system to monitor locomotor behavior in group-housed vervets in the Vervet Research Colony at Wake Forest. This will allow us to monitor position within the home environment longitudinally for long periods of time (weeks to months) and will allow us to determine whether locomotor behavior in aging vervets displays patterns characteristic of dementia-associated "wandering" in humans. We will also measure hippocampal volume with structural MRI and metabolic activity with FDG-PET imaging, and Alzheimer's- related blood biomarkers. This will allow us to explore whether any features of movement around the home enclosure discriminate between individuals based on hippocampal volume, glucose metabolic rate, or fluid biomarkers of Alzheimer's disease. Because behavioral readouts of hippocampal function currently are mainly obtained through prolonged cognitive testing, which is resource-intensive and impractical to apply across large groups of primates, this proposal has the potential to uncover behavioral measures that can be continuously acquired and analyzed in real time and over a period of months to years that signal hippocampal dysfunction with aging and neuropathology in vervet monkeys. This will open new possibilities for using this model species to study interventions that may offset the development of Alzheimer's pathology in humans during the earliest phases of the disease.

项目摘要 黑长尾猴（Chlorocebus aethiops sabaeus）出现与年龄相关的淀粉样蛋白病理学， 人类阿尔茨海默病的早期阶段。海马神经元代谢减退和体积减少发生在 人类遗忘型轻度认知障碍，一种以日常记忆受损为特征的病症， 通常早于阿尔茨海默病的发展，但年龄对长尾猴海马功能的影响是 不知道。确定年龄和阿尔茨海默病相关生物标志物如何与海马神经元相关 结构和功能将大大提高该物种作为年龄模型的实用性- 相关的认知障碍和早期阿尔茨海默病。作为第一个探索性的步骤， 表征海马结构和功能在老龄长尾猴，本申请的目标是开发一个 一个连续跟踪系统，用于监测Vervet研究中群体饲养的Vervet的运动行为 在维克森林的殖民地。这将使我们能够纵向监测家庭环境中的位置， 长时间（几周到几个月），并将使我们能够确定是否运动行为在老化 长尾猴表现出与人类痴呆症相关的“游荡”特征。我们还将测量 海马体积与结构MRI和代谢活动与FDG-PET成像，和阿尔茨海默氏症- 相关血液生物标志物。这将使我们能够探索是否有任何功能的运动在家里 根据海马体积、葡萄糖代谢率或液体， 阿尔茨海默病的生物标志物。因为海马功能的行为读数目前主要是 通过长时间的认知测试获得，这是资源密集型的，不切实际的，适用于大规模的 灵长类动物群体，这一建议有可能揭示行为措施，可以连续 在真实的时间和数月至数年的时间内获得并分析海马功能障碍的信号 衰老和神经病理学的关系。这将为使用这种模式物种开辟新的可能性 研究干预措施，可能抵消人类阿尔茨海默病的病理发展， 疾病的阶段。