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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

基本信息

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
项目类别：
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&apos s Disease Alzheimer&apos 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

项目摘要

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.

简介: