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: 10285192
• 负责人: Matthew Jorgensen
• 金额: $ 35.23万
• 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/10285192
• 关键词: Administrative Supplement; Affect; African Green Monkey; Age; Agonist; Alzheimer' s Disease; Alzheimer' s disease diagnosis; Alzheimer' s disease model; Alzheimer' s disease patient; Alzheimer’s disease biomarker; Amyloid beta-42; Amyloid beta-Protein; Animals; Apoptosis; Archives; Behavioral; Beta Cell; Biological; Biological Markers; Biomedical Research; Brain; Categories; Cerebrum; Clinical; Cognitive; Cognitive deficits; Communities; Consultations; Coupled; Data; Dementia; Development; Elderly; Exocytosis; Future; G-Protein-Coupled Receptors; GCG gene; GPR119 receptor; Gene Expression Profile; Glucagon; Glucose; Glycoproteins; Glycosylated hemoglobin A; Goals; Grant; Hippocampus (Brain); Human; Hyperinsulinism; Image; Impaired cognition; In Vitro; Insulin; Insulin Resistance; Isotopes; Measures; Memory; Modeling; Nature; Nervous System Physiology; Neurodegenerative Disorders; Neurologic; Non-Insulin-Dependent Diabetes Mellitus; Pathogenesis; Pathologic; Pathology; Positron-Emission Tomography; Presynaptic Terminals; Process; Production; Quality of life; Radiolabeled; Regulatory Pathway; Reporting; Research; Resources; Sampling; Senile Plaques; Specificity; Structure; Synapses; Synaptic Vesicles; Temporal Lobe; Tracer; Training; Triazoles; United States National Institutes of Health; Validation; Variant; X-Ray Computed Tomography; age related; base; biomedical resource; brain volume; cingulate gyrus; clinical imaging; clinically relevant; cognitive function; cohort; daily functioning; density; design; frontal lobe; glucose metabolism; human disease; human model; imaging agent; imaging biomarker; imaging properties; imaging study; improved; in vivo; insulin secretion; learning ability; molecular imaging; motor deficit; nonhuman primate; novel; pre-clinical; radiotracer; receptor; research study; response; small molecule; specific biomarkers; tau aggregation; translational model; vervet

PROJECT SUMMARY Alzheimer’s disease (AD) is the most common neurodegenerative disease causing dementia in the elderly. Vervets/African green monkeys are an excellent nonhuman primate model to study the various pathological changes associated with progression of AD. In recent years, there has been a paradigm shift for the diagnosis of AD using molecular imaging of AD-specific biomarkers via positron emission tomography (PET). Reduction of several biomarkers are implicated in early stages of AD pathogenesis. For example, loss of (a) G-coupled receptor proteins including GPR119 in insulin-triggered regulatory pathways and (b) synaptic density including synaptic vesicle 2A (SV2A) levels are associated with severe cognitive decline processes in the neurological cascade of AD. A key unanswered question is whether the quantitative nature of PET can be used to measure the in vivo concentrations of GPR119 and SV2A in AD. Our goal in this supplement is to develop and validate GPR119 and SV2A as novel imaging biomarkers in a vervet model of AD. In Aim 1, we will develop two potential triazole-based GPR119 agonists and radiolabel them with [11C] and [18F] PET isotopes. GPR119 imaging properties of both the radiotracers will be evaluated in a cohort vervets with variation in age, HbA1c and archived CSF Aβ levels. In Aim 2, we will validate the synaptic density measuring parameters of an established SV2A PET imaging radiotracer, [11C]UCB-J, in the same cohort of vervets from Aim 1. The PET imaging data described here will be used as the basis for a future R01 application that further expands the use of the vervet model of AD.

项目概要 阿尔茨海默病（AD）是导致老年人痴呆的最常见神经退行性疾病。 黑长尾黑猴/非洲绿猴是研究各种病理学的优秀非人类灵长类动物模型 与 AD 进展相关的变化。近年来，诊断范式发生了转变 通过正电子发射断层扫描 (PET) 对 AD 特异性生物标志物进行分子成像，从而对 AD 进行诊断。减少 多种生物标志物与 AD 发病机制的早期阶段有关。例如，(a) G 耦合的损失 受体蛋白（包括胰岛素触发的调节途径中的 GPR119）和 (b) 突触密度，包括 突触小泡 2A (SV2A) 水平与神经系统严重认知衰退过程相关 AD 级联。一个尚未解答的关键问题是 PET 的定量性质是否可以用来测量 AD 中 GPR119 和 SV2A 的体内浓度。我们在本补充中的目标是开发和验证 GPR119 和 SV2A 作为 AD 黑长尾猴模型中的新型成像生物标志物。在目标 1 中，我们将开发两个 潜在的基于三唑的 GPR119 激动剂，并用 [11C] 和 [18F] PET 同位素对其进行放射性标记。探地雷达119 两种放射性示踪剂的成像特性将在年龄、HbA1c 变化的长尾黑颚猴队列中进行评估 和存档的 CSF Aβ 水平。在目标 2 中，我们将验证突触密度测量参数 在来自目标 1 的同一组长尾黑颚猴中建立了 SV2A PET 成像放射性示踪剂 [11C]UCB-J。 这里描述的成像数据将用作未来 R01 应用的基础，进一步扩展用途 AD 的长尾黑颚猴模型。