Neurophysiological Basis for Functional Connectivity Changes in Early Alzheimer’s Disease
早期阿尔茨海默病功能连接变化的神经生理学基础
基本信息
- 批准号:10534529
- 负责人:
- 金额:$ 4.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:APP-PS1AcuteAddressAffectAge-MonthsAgingAlzheimer disease detectionAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAlzheimer’s disease biomarkerAmyloidAmyloid beta-ProteinAnimalsBasic ScienceBrainCalciumCharacteristicsChronicClinicalClinical SciencesCognitionCognitiveConcentration measurementDataDementiaDevelopmentDiseaseDisease ProgressionDoseEarly DiagnosisEarly InterventionEarly treatmentEventExhibitsFluorescence MicroscopyFunctional disorderGlutamatesGlutamineGrowthHumanHyperactivityImageImpaired cognitionIndividualMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMeasuresMemory impairmentMentorsMicroscopicMultimodal ImagingMusNerve DegenerationNeurodegenerative DisordersNeurologyNeuronsNeurotransmittersOpticsPathologyPatientsPhasePhysiciansPhysiologicalResearch TrainingRiskRodentRoleScientistSignal TransductionSpecificitySpectrum AnalysisSymptomsSynapsesTechnical ExpertiseTechniquesTestingTrainingTranslationsUnited StatesWild Type MouseWorkYangabeta accumulationawakebasecalcium indicatorcareerclinical developmentclinically relevantearly detection biomarkersexcitotoxicityexperienceexperimental studyextracellularhuman imaginghuman subjectimaging approachin vivoin vivo fluorescenceinterestmouse modelneuroimagingneuronal circuitryneuropathologyneurophysiologynoveloptical imagingoptical sensorpredictive markerresponsesensortau Proteinstau-1treatment strategytwo photon microscopytwo-photon
项目摘要
Abstract
Early diagnosis and treatment of Alzheimer’s disease (AD) are critical for delaying the onset of clinical symptoms,
such as cognitive impairments and memory deficits. Early in AD, cognitively normal individuals who are positive
for amyloid-β, a predictive biomarker of AD, exhibit a transient increase in brain connectivity prior to a decline in
brain connectivity and cognition. This hyper-connectivity phase of AD suggests a prodromal pathology that may
be exploited as an early biomarker prior to the onset of clinical symptoms. Though these changes in brain
network connectivity have been well documented, little is known about the underlying neuropathology. I seek to
test whether localized increases in excitatory neuronal activity caused by amyloid-β drive the brain-wide hyper-
connectivity observed in early AD. I will use a multimodal imaging approach to determine the impact of amyloid-
β on neuronal and glutamate activity on the scale of the neuron (microscopic), regional neuronal circuit
(mesoscopic), and inter-regional network connectivity (macroscopic) in mouse models of AD. My proposal
comprises the following three aims: Aim 1: Determine the impact of acute exposure of amyloid-β on neuronal,
glutamate, and network activity in the normal cortex, Aim 2: Determine the impact of chronic, progressive
amyloid-β accumulation on neuronal, glutamate, and network activity in a young mouse model of AD, and Aim
3: Determine how total glutamate concentration changes, measured by translational magnetic resonance
spectroscopy, relate to synaptic glutamate activity changes with disease progression. Together, these
experiments could determine the neurophysiological underpinnings of the connectivity changes observed in early
AD. Data from this study could introduce novel treatment strategies for patients at risk of developing AD.
Furthermore, this work closely integrates my clinical interest in neuroimaging and neurology. In addition to
rigorous mentored research training, this proposal includes clinical experience and professional development
that will facilitate my growth into an independent physician-scientist.
摘要
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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Christopher Gregory Cover其他文献
Christopher Gregory Cover的其他文献
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{{ truncateString('Christopher Gregory Cover', 18)}}的其他基金
Neurophysiological Basis for Functional Connectivity Changes in Early Alzheimer’s Disease
早期阿尔茨海默病功能连接变化的神经生理学基础
- 批准号:
10710379 - 财政年份:2022
- 资助金额:
$ 4.8万 - 项目类别:
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