Locus Coeruleus Biomarker Development for Early Detection of Alzheimers Disease in Humans
用于早期检测人类阿尔茨海默病的蓝斑生物标记物开发
基本信息
- 批准号:10380028
- 负责人:
- 金额:$ 16.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AccelerationAddressAffectAgeAgingAlzheimer disease detectionAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAlzheimer&aposs disease patientAnti-Inflammatory AgentsBackBasic ScienceBlood - brain barrier anatomyBrainBrain regionCatecholaminesCell DensityCell NucleusChronologyClinicalCognitionCognitiveData SetDetectionDevelopmentDiagnosisDiseaseDisease ProgressionDopamineEarly DiagnosisEarly identificationElderlyFinancial compensationFoundationsHealthHumanImageIndividualIndividual DifferencesInfrastructureInjuryMagnetic ResonanceMagnetic Resonance ImagingMaintenanceMeasuresMedialMediatingMemoryMental disordersMetabolismMethodsMidbrain structureModelingNerve DegenerationNeuromodulatorNorepinephrineOxidative StressParkinson DiseaseParticipantPathologicPathologyPatientsPatternPerformancePlayPositron-Emission TomographyProcessPropertyRadioactive TracersReportingResearchResearch PersonnelResolutionRoleSignal TransductionSleepSourceStressStructureSubstantia nigra structureSymptomsSystemTemporal LobeTestingTherapeutic InterventionTyrosineValidationabnormally phosphorylated tauamyloid pathologybiomarker developmentcognitive neuroscienceefficacy testinghealthy aginghyperphosphorylated tauimaging approachimaging biomarkerimaging modalityin vivointerestlocus ceruleus structuremild cognitive impairmentmultimodal neuroimagingneurochemistryneuroimagingneuromelaninneuroregulationnorepinephrine systempars compactapredictive markerresiliencetargeted treatmenttau Proteinstau aggregationtheoriestoolyoung adult
项目摘要
Project Summary
The advent of neuroimaging methods for measuring locus coeruleus (LC) structural
integrity has generated intense interest from scientific fields focused on Alzheimer’s
disease (AD), psychiatric disorders, as well as basic cognitive neuroscience. The LC is
the brain’s primary generator of the neuromodulator norepinephrine (NE) and is one of
the first brain regions to accumulate hyperphosphorylated tau protein, a hallmark
pathological agent in AD. The ability to use magnetic resonance (MR) imaging to assess
LC integrity opens up exciting possibilities for earliest detection of disease acceleration,
and may also provide an MR measure that captures information about individual
differences in neurochemical function. The ability to study neurochemical systems in vivo
in humans is limited, with imaging approaches using radioactive tracers being the most
established (e.g. positron emission tomography (PET)). However, due to the burden to
subjects, as well as the infrastructural challenges, PET imaging is not a tool many
researchers use despite the central role neuromodulatory systems like NE play in basic
cognition and disease. We will take initial steps towards testing the validity of LC MR
measures for predicting NE function by examining the correspondence between a
neuromelanin-sensitive MR measure of LC integrity and a PET measure of
catecholamine (norepinephrine/dopamine) synthesis capacity ([18F]Fluoro-l-m-tyrosine
(FMT)) within subject in healthy young and older adults (Aim 1). Accumulating evidence
in healthy aging, AD, and Parkinson’s disease suggests the catecholamine system
responds to injury and shows compensatory capacity. Next, we will test the hypothesis
that with advancing age, catecholamine synthesis goes up (Aim 2). Finally, to test the
utility of LC neuroimaging measures as forecasters of the advancement of tau pathology,
we will explore whether neuromelanin-sensitive MR and [18F]FMT predict the
accumulation of tau in the medial temporal lobe using tau-sensitive [18F]flortaucipir
imaging (Aim 3). Together, this research takes critical steps in establishing MR
approaches as sensitive to neurochemical function, examines intriguing mechanisms of
neurochemical compensation, and provides empirical testing of models of pathological
spread in AD.
项目摘要
测量蓝斑(LC)结构的神经成像方法的出现
诚信引起了专注于阿尔茨海默氏症的科学领域的强烈兴趣
疾病(AD)、精神疾病以及基础认知神经科学。述LC
脑中神经调节剂去甲肾上腺素(NE)的主要产生者,
最先积累过度磷酸化tau蛋白的大脑区域,
AD中的病理因子。使用磁共振(MR)成像评估
LC完整性为疾病加速的最早检测开辟了令人兴奋的可能性,
并且还可以提供捕获关于个体的信息的MR测量
神经化学功能的差异。研究活体神经化学系统的能力
在人类中是有限的,使用放射性示踪剂的成像方法是最
建立(例如正电子发射断层扫描(PET))。然而,由于负担,
主题,以及基础设施的挑战,PET成像是不是一个工具,许多
尽管NE等神经调节系统在基础免疫中发挥着重要作用,
认知与疾病我们将采取初步措施,测试LC MR的有效性
用于通过检查A和B之间的对应性来预测NE功能的措施
神经黑色素敏感的LC完整性MR测量和PET测量
儿茶酚胺(去甲肾上腺素/多巴胺)合成能力([18F]氟-l-m-酪氨酸
(FMT))在健康年轻人和老年人中的受试者(目标1)。越来越多的证据
在健康老龄化、AD和帕金森病中,
对损伤作出反应并显示出补偿能力。接下来,我们将测试假设
随着年龄的增长,儿茶酚胺的合成增加(目标2)。最后,为了测试
LC神经成像测量作为tau病理学进展的预测者的效用,
我们将探讨神经黑素敏感的MR和[18 F]FMT是否能预测
使用tau-敏感的[18F]flortaucipir在内侧颞叶中的tau积累
成像(Aim 3)。总之,这项研究采取了关键步骤,建立MR
方法敏感的神经化学功能,检查有趣的机制,
神经化学补偿,并提供病理模型的实证检验
在AD中传播。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Locus coeruleus catecholamines link neuroticism and vulnerability to tau pathology in aging.
- DOI:10.1016/j.neuroimage.2022.119658
- 发表时间:2022-11
- 期刊:
- 影响因子:5.7
- 作者:Parent, Jourdan H.;Ciampa, Claire J.;Harrison, Theresa M.;Adams, Jenna N.;Zhuang, Kailin;Betts, Matthew J.;Maass, Anne;Winer, Joseph R.;Jagust, William J.;Berry, Anne S.
- 通讯作者:Berry, Anne S.
Interactive effects of locus coeruleus structure and catecholamine synthesis capacity on cognitive function.
- DOI:10.3389/fnagi.2023.1236335
- 发表时间:2023
- 期刊:
- 影响因子:4.8
- 作者:
- 通讯作者:
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{{ truncateString('Anne Shively Berry', 18)}}的其他基金
Dopaminergic mechanisms of resilience to Alzheimer's disease neuropathology
阿尔茨海默病神经病理学恢复的多巴胺能机制
- 批准号:
10809199 - 财政年份:2023
- 资助金额:
$ 16.25万 - 项目类别:
Upregulated Norepinephrine Synthesis Capacity in Aging
衰老过程中去甲肾上腺素合成能力上调
- 批准号:
10447225 - 财政年份:2022
- 资助金额:
$ 16.25万 - 项目类别:
Upregulated Norepinephrine Synthesis Capacity in Aging
衰老过程中去甲肾上腺素合成能力上调
- 批准号:
10629346 - 财政年份:2022
- 资助金额:
$ 16.25万 - 项目类别:
Locus Coeruleus Biomarker Development for Early Detection of Alzheimers Disease in Humans
用于早期检测人类阿尔茨海默病的蓝斑生物标记物开发
- 批准号:
10194679 - 财政年份:2021
- 资助金额:
$ 16.25万 - 项目类别:
Age effects on memory and reward systems in decision making
年龄对决策中的记忆和奖励系统的影响
- 批准号:
10187476 - 财政年份:2019
- 资助金额:
$ 16.25万 - 项目类别:
Dopaminergic modulation of networks mediating cognitive flexibility in older adul
介导老年人认知灵活性的网络多巴胺能调节
- 批准号:
8874736 - 财政年份:2014
- 资助金额:
$ 16.25万 - 项目类别:
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