Relationships between blood-brain barrier breakdown, Alzheimer's disease pathology, and memory in aging
血脑屏障破坏、阿尔茨海默病病理学和衰老记忆之间的关系
基本信息
- 批准号:10387988
- 负责人:
- 金额:$ 4.27万
- 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 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAgeAgingAlbuminsAlzheimer disease detectionAlzheimer&aposs DiseaseAlzheimer&aposs disease pathologyAlzheimer’s disease biomarkerAmyloidAmyloid beta-ProteinAppearanceAreaAtrophicBloodBlood - brain barrier anatomyBlood TestsBlood VesselsBrainBrain regionClinicalCognitionCognitiveCommunicationCross-Sectional StudiesData AnalysesDepositionDetectionDevelopmentDiagnosisDiseaseEarly DiagnosisEarly InterventionEducational process of instructingElderlyEpisodic memoryEtiologyEventExtravasationFellowshipFunctional disorderGoalsHippocampus (Brain)HomeHomeostasisHumanImpaired cognitionImpairmentInferiorInstitutesLeadLongitudinal StudiesMagnetic Resonance ImagingMeasuresMedialMediatingMemoryMentorsMethodsMultimodal ImagingNerve DegenerationNeuronal InjuryNeuropsychological TestsNeurosciencesOutcomePathogenesisPathologicPathologic ProcessesPathologyPathway interactionsPatientsPerformancePositron-Emission TomographyPostdoctoral FellowProteinsResearchResearch PersonnelResearch Project GrantsResearch TrainingRoleSamplingSecureStudentsSymptomsTemporal LobeTestingTracerTrainingVascular Diseasesabeta accumulationabeta depositionage relatedbaseblood-brain barrier disruptionblood-brain barrier permeabilizationcareercareer developmentcerebral atrophycontrast enhanceddesignearly detection biomarkershealthy agingimaging biomarkerimaging facilitiesimaging modalityin vivoinnovationinsightmultimodal neuroimagingneuroimagingneurotoxicneurovascularnormal agingnovelpharmacokinetic modelprotein aggregationskillsstatisticstau Proteinstau aggregationtheoriestherapy developmenttreatment strategyvascular injuryyoung adult
项目摘要
Project Summary
The major theory of causation for Alzheimer’s disease (AD) is deposition of the protein β-amyloid, however it is
unclear how aging influences amyloid accumulation or why cognitive decline can occur in its absence. Evidence
suggests that neurovascular dysfunction, such as the breakdown of the blood-brain barrier (BBB), is related to
neurodegeneration and cognitive impairment, and that this relationship may occur independently of amyloid.
However, the direct relationship between BBB breakdown and AD biomarkers, as well as cognition, has not been
thoroughly investigated in humans. The aim of this study is to use a novel multi-modal imaging design to examine
how BBB breakdown in humans is related to AD biomarkers of atrophy, amyloid and tau, and cognition. BBB
breakdown will be quantified in vivo using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI),
which allows for the detection of subtle BBB leakage in the human brain. Both tau and Aβ will be measured in
vivo using the positron emission tomography (PET) tracers [18F] Flortaucipir and [11C] PiB, respectively.
Neurodegeneration will be measured with structural MRI and episodic memory with a composite
neuropsychological test score. Aim 1 will determine if BBB breakdown increases with age and if there are specific
regions that are more vulnerable during normal aging. Aim 2 will examine if BBB breakdown in the temporal lobe
is related to greater global Aβ and regional tau. In addition, it will be determined if BBB breakdown is associated
with greater retrospective longitudinal Aβ and tau accumulation. Finally, Aim 3 will determine if BBB breakdown
in the temporal lobe is related to smaller temporal lobe volumes and worse memory performance. Relationships
between BBB breakdown and retrospective longitudinal change in memory performance, independent of amyloid
and tau, will also be examined. The findings from this study will help unravel fundamental mechanisms of AD
pathogenesis in the human brain, which has vital implications for early detection and the development of new
treatment strategies for AD. The proposed research project will achieve the applicant’s training goals, which
include (1) developing skills in multimodal imaging, (2) advanced statistics and data analysis training, (3) training
in clinical impairment and pathophysiology of AD, (4) development of teaching and mentoring skills, (5)
improvement of effective scientific communication skills, and (6) career development. UC Berkeley’s Helen Wills
Neuroscience Institute is home to a network of cutting-edge researchers and world-class imaging facilities. The
sponsor of the project, Dr. William Jagust, is at the forefront in applying multimodal neuroimaging methods to
study questions of aging and AD. He also has successfully mentored numerous students in the past, who have
become leaders in the field. The co-sponsor, Dr. Suzanne Baker, is an expert in optimization of neuroimaging
quantification for both PET and MRI, as well as pharmacokinetic modeling. Both the proposed research and the
training plan will provide the applicant with the skillset to secure a competitive post-doctoral fellowship and a
successful research career studying aging and AD.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Marisa Nicole Denkinger其他文献
Marisa Nicole Denkinger的其他文献
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{{ truncateString('Marisa Nicole Denkinger', 18)}}的其他基金
Relationships between blood-brain barrier breakdown, Alzheimer's disease pathology, and memory in aging
血脑屏障破坏、阿尔茨海默病病理学和衰老记忆之间的关系
- 批准号:
10799538 - 财政年份:2022
- 资助金额:
$ 4.27万 - 项目类别:
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