Nanoparticles for detecting noradrenergic neurons in Alzheimer's Disease

用于检测阿尔茨海默氏病去甲肾上腺素能神经元的纳米颗粒

• 批准号: 10080203
• 负责人: Puliyur MohanKumar
• 金额: $ 26.67万
• 依托单位: S G ENDOCRINE RESEARCH LLC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10080203
• 关键词: Affect; Age; Alzheimer' s Disease; Alzheimer' s disease model; American; Amino Acid Neurotransmitters; Amyloid beta-Protein; Anabolism; Animal Model; Area; Arousal; Basal Nucleus of Meynert; Behavioral; Biological; Biopsy; Blood - brain barrier anatomy; Brain; Brain Stem; Brain imaging; Cannulas; Caregivers; Catecholamines; Cerebral cortex; Characteristics; Cognition; Cognitive; Cognitive deficits; Contrast Media; Cost of Illness; Diagnosis; Disease; Disease Progression; Early Diagnosis; Early treatment; Economic Burden; Functional disorder; Goals; Healthcare Systems; High Pressure Liquid Chromatography; Hippocampus (Brain); Human; Human Amyloid Precursor Protein; Image; Levodopa; Ligands; Magnetic Resonance Imaging; Magnetism; Measures; Memory Loss; Mental disorders; Methods; Modality; Monitor; Nanostructures; Near-infrared optical imaging; Nerve Degeneration; Neurocognitive; Neurocognitive Deficit; Neurodegenerative Disorders; Neurofibrillary Tangles; Neurons; Neurotransmitters; Norepinephrine; Operative Surgical Procedures; Optics; Outcome; Pathologic; Pathology; Patients; Phase; Phenylalanine; Positron-Emission Tomography; Pre-Clinical Model; Preclinical Testing; Process; Property; Prosencephalon; Quality of life; Rattus; Research; Resolution; Sampling; Small Business Technology Transfer Research; Structure; Testing; Thalamic structure; Therapeutic Intervention; Three-Dimensional Imaging; Tissues; Translating; Wakefulness; age related; base; biomaterial compatibility; cholinergic; cost effective; design; economic impact; hindbrain; imaging agent; imaging capabilities; imaging modality; implantation; innovation; locus ceruleus structure; mutant; nanoparticle; nerve supply; nervous system disorder; neurobehavioral; non-invasive imaging; non-invasive monitor; noradrenergic; novel; particle; presenilin-1; tau Proteins; temporal measurement; tool

Summary: Alzheimer's disease (AD) is a progressive neurological disorder that is marked by the presence of amyloid-ß plaques, neurofibrillary tangles and cognitive deficits. The economic impact of this disease is staggering and is expected to exceed $1 trillion dollars by the year 2050. Early diagnosis and treatment can substantially reduce the economic burden related to AD. Specifically, being able to assess early pathological changes in specific brain areas could be beneficial for diagnosis and treatment. The locus coeruleus (LC), which provides the majority of the noradrenergic innervation to areas such as thalamus, cortex and hippocampus, undergoes extensive neurodegenerative changes. These changes that occur in the LC have been described as the earliest pathologies observed in AD and, critically, appear at least a decade ahead of the neurocognitive deficits. LC noradrenergic neurons are involved in regulating key neurobehavioral functions such as cognition, arousal and wakefulness. However, assessing changes in LC over the course of AD in patients remains a major challenge. The main objective of the proposed research in phase 1 is to develop an organic nanoparticle-based MRI imaging agent to non-invasively monitor noradrenergic neurons in the LC using a preclinical model of AD. Our preliminary studies provide evidence that these nanoparticles are taken by noradrenergic neurons in the brainstem and facilitate the imaging process. Our specific aims are to 1. To assess the ability of the nanoparticles to image the LC using MRI, and correlate with changes in norepinephrine levels. 2. To assess whether these particles can be used to measure degenerative changes as the disease progresses. Translating this to larger animal models and conducting preclinical testing will be next step following this STTR.

概括： 阿尔茨海默氏病（AD）是一种进行性神经系统疾病，以此为标志 淀粉样蛋白斑块，神经原纤维缠结和认知缺陷的存在。 这种疾病的经济影响令人惊讶，预计将超过1万亿美元 到2050年的美元。早期诊断和治疗可以大大减少 与广告有关的经济燃烧。特别是能够评估早期病理 特定大脑区域的变化可能对诊断和治疗有益。这 基因座（LC），它提供了大多数去甲肾上腺素的神经支配 丘脑，皮层和海马等地区经历了广泛的经历 神经退行性变化。 LC中发生的这些变化已被描述 作为最早在AD中观察到的病理，至少是十年 在神经认知缺陷之前。 LC NORADENAGIC神经元参与 调节关键的神经行为功能，例如认知，唤醒和清醒。 但是，在患者中评估LC在AD过程中的变化仍然是主要的 挑战。 第1阶段拟议研究的主要目的是开发有机 基于纳米颗粒的MRI成像剂，用于非侵入性监测去甲肾上腺素能神经元 在LC中使用AD的临床前模型。我们的初步研究提供了证据表明 这些纳米颗粒是由脑干中的肾上腺素神经元采集的，并制备了 成像过程。我们的具体目的是1。评估 纳米颗粒使用MRI对LC进行成像，并与去甲肾上腺素的变化相关 水平。 2。评估这些粒子是否可以用于测量退化 随着疾病进展的变化。将其转换为较大的动物模型和 在此STTR之后，进行临床前测试将是下一步。