Nanoparticles for detecting noradrenergic neurons in Alzheimer's Disease
Nanoparticles for detecting noradrenergic neurons in Alzheimer's Disease
批准号:
10080203
负责人:
Puliyur MohanKumar
金额:
$26.67万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-08-15 至 2023-07-31
关键词:
AffectAgeAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAmericanAmino Acid NeurotransmittersAmyloid beta-ProteinAnabolismAnimal ModelAreaArousalBasal Nucleus of MeynertBehavioralBiologicalBiopsyBlood - brain barrier anatomyBrainBrain StemBrain imagingCannulasCaregiversCatecholaminesCerebral cortexCharacteristicsCognitionCognitiveCognitive deficitsContrast MediaCost of IllnessDiagnosisDiseaseDisease ProgressionEarly DiagnosisEarly treatmentEconomic BurdenFunctional disorderGoalsHealthcare SystemsHigh Pressure Liquid ChromatographyHippocampus (Brain)HumanHuman Amyloid Precursor ProteinImageLevodopaLigandsMagnetic Resonance ImagingMagnetismMeasuresMemory LossMental disordersMethodsModalityMonitorNanostructuresNear-infrared optical imagingNerve DegenerationNeurocognitiveNeurocognitive DeficitNeurodegenerative DisordersNeurofibrillary TanglesNeuronsNeurotransmittersNorepinephrineOperative Surgical ProceduresOpticsOutcomePathologicPathologyPatientsPhasePhenylalaninePositron-Emission TomographyPre-Clinical ModelPreclinical TestingProcessPropertyProsencephalonQuality of lifeRattusResearchResolutionSamplingSmall Business Technology Transfer ResearchStructureTestingThalamic structureTherapeutic InterventionThree-Dimensional ImagingTissuesTranslatingWakefulnessage relatedbasebiomaterial compatibilitycholinergiccost effectivedesigneconomic impacthindbrainimaging agentimaging capabilitiesimaging modalityimplantationinnovationlocus ceruleus structuremutantnanoparticlenerve supplynervous system disorderneurobehavioralnon-invasive imagingnon-invasive monitornoradrenergicnovelparticlepresenilin-1tau Proteinstemporal measurementtool
中文摘要
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。
英文摘要
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.
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