Squirrel Monkey Breeding and Research Resource - Administrative Supplement (Cognitive Development)

项目摘要 阿尔茨海默病（AD）是一种主要的健康问题，其定义为大脑中的病理变化， 与行为和认知功能的改变相一致。许多人认为灵长类动物 AD模型，因为它们自然地再现了AD的一些神经病理学特征， 而其它模式生物（即，啮齿类动物）不。例如，当淀粉样蛋白β（Aβ）沉积发生时， 在大多数哺乳动物中，仅在少数非人类中鉴定出tau阳性神经元缠结（NFT 迄今为止研究过的物种。此外，来自几个不同属的老年非人灵长类动物， 脑淀粉样血管病（CAA），一种在80%的AD患者中发现的神经血管疾病， 认知能力下降在这里，我们建议将松鼠猴作为当前和 衰老生物学和AD研究的未来研究。具体来说，我们建议培训一批 社会生活的松鼠猴对使用自动认知测试系统（automated cognitive testing system，简称css）的研究， 评估各种认知功能，包括学习、记忆和执行控制。创建大型 接受过这种系统训练的松鼠猴群将为动物提供已建立的认知能力， 表型用于临床前研究，并允许检查其与潜在年龄相关的 神经解剖学、神经病理学和生物标志物数据的差异。此外，我们还将测试 老年痴呆症的经历会影响与年龄相关的灰质体积和白色物质完整性的变化。 将从20只接受过训练的老年和老年猴中获得磁共振图像（MRI）。 以及20只年龄性别匹配的对照组猴子，这些猴子没有接受过训练。为了检验学习是否 使用一种能减缓正常大脑衰老过程的方法，我们将比较灰质体积和白色 使用基于体素的形态测定法，研究对象和对照组猴子之间的物质完整性。如果认知 晚年的刺激保持认知功能并抑制皮质组织的变化率， 那么我们假设，黑猴的灰质体积和白色物质的完整性会增加， 大脑中对衰老敏感的区域拟议的研究，在其整体，将填补一个重要的空白，在我们的 关于松鼠猴衰老和认知的比较生物学知识，也将创造一个 为未来临床前研究提供宝贵的非人灵长类动物资源。

Project Summary Alzheimer’s disease (AD) is a major health concern defined by pathologic changes in the brain that coincide with altered behavior and cognitive function. Many have suggested that there is a need for primate models of AD because they naturally recapitulate some neuropathological features of AD with advanced age whereas other model organisms (i.e., rodents) do not. For instance, while amyloid-beta (Aβ) deposition occurs in most mammals, tau-positive neurofibrillary tangles (NFT) have only been identified in a few nonhuman species studied to date. Additionally, elderly nonhuman primates from several different Genera, develop cerebral amyloid angiopathy (CAA), a neurovascular condition found in 80% of AD patients and associated with cognitive decline. Here, we are proposing to develop squirrel monkeys as a model species for current and future studies on the biology of aging and AD research. Specifically, we propose to train a cohort of group socially-living squirrel monkeys on the use of an automated cognitive testing system (ACTS) that is designed to assess a variety of cognitive functions including learning, memory and executive control. Creating large cohorts of squirrel monkeys trained on the ACTS system will provide animals with established cognitive phenotypes for use in preclinical studies and allow for examining their association with potential age-related differences in neuroanatomical, neuropathological and biomarker data. In addition, we will test whether experience with an ACTS influences age-related changes in gray matter volume and white matter integrity. Magnetic resonance images (MRI) will be obtained from 20 elderly and geriatric monkeys trained on the ACTS and 20 age-sex matched control monkeys that were not trained on the ACTS. To examine whether learning to use an ACTS slows down the normal brain aging process, we will compare gray matter volume and white matter integrity between the ACTS and control monkeys using voxel-based morphometry. If cognitive stimulation late in life preserves cognitive functioning and inhibits rates of change in cortical organization, then we hypothesize that ACTS monkeys will have increased gray matter volume and white matter integrity in brain regions sensitive to aging. The proposed studies, in their entirety, will fill an important gap in our knowledge about the comparative biology of aging and cognition in squirrel monkeys and will also create an invaluable nonhuman primate resource for future use preclinical studies.