Nanoparticles for detecting noradrenergic neurons in Alzheimer's Disease

总结： 阿尔茨海默氏病（AD）是一种进行性神经系统疾病，其特征在于： 存在淀粉样蛋白斑块、神经纤维缠结和认知缺陷。的 这种疾病的经济影响是惊人的，预计将超过1万亿美元 美元到2050年。早期诊断和治疗可以大大减少 与AD相关的经济负担。具体来说，能够评估早期病理性 特定脑区的变化可能有利于诊断和治疗。的 蓝斑（LC），它提供了大部分的去甲肾上腺素能神经支配， 丘脑、皮层和海马等区域， 神经退行性改变已经描述了LC中发生的这些变化 作为AD中观察到的最早的病理学， 在神经认知缺陷之前。LC去甲肾上腺素能神经元参与 调节关键的神经行为功能，如认知、唤醒和觉醒。 然而，在AD患者中评估LC在病程中的变化仍然是一个主要的问题。 挑战. 第一阶段拟议研究的主要目标是开发一种有机的 用于非侵入性监测去甲肾上腺素能神经元的基于纳米颗粒的MRI成像剂 在LC中使用AD的临床前模型。我们的初步研究提供了证据， 这些纳米颗粒被脑干中的去甲肾上腺素能神经元摄取， 成像过程。我们的具体目标是1.为了评估 使用MRI对LC进行成像，并与去甲肾上腺素的变化相关 程度. 2.为了评估这些颗粒是否可用于测量退行性变 随着疾病的发展而变化。将其转化为更大的动物模型， 进行临床前试验将是本STTR之后的下一步。

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.