Integrative analysis of multi-omics data to delineate CCL2 associated inflammatory pathways in Alzheimers Disease
多组学数据综合分析以描绘阿尔茨海默病中 CCL2 相关炎症通路
基本信息
- 批准号:10369676
- 负责人:
- 金额:$ 16.1万
- 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:2021-03-15 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:AccountingAcuteAddressAffectAgeAge-YearsAlzheimer&aposs DiseaseAlzheimer&aposs disease brainAlzheimer&aposs disease modelAlzheimer&aposs disease patientAlzheimer&aposs disease riskAmyloidAnatomyAnimal ModelAreaAutomobile DrivingBehavioralBioinformaticsBiologicalBiological FactorsBiological MarkersBrainCCL2 geneCause of DeathCellsCerebrospinal FluidClinicalClinical dementia rating scaleCognitiveDataDatabasesDementiaDiseaseDisease ProgressionEducationFlow CytometryFoundationsFutureGenesGeneticGenetic PolymorphismGenomicsGoalsHeterogeneityHumanImmuneImmune System DiseasesImmune systemImpaired cognitionIndividualInflammationInflammatoryInflammatory ResponseInterventionInvestigationKnowledgeLeukocytesMMP3 geneMediatingMedicineMicrogliaModelingMolecularMultiomic DataNerve DegenerationNeuraxisNeurodegenerative DisordersNeurogliaOutcomeOutcomes ResearchPathologyPathway interactionsPatientsPeripheralPersonsPhenotypePlasmaPredictive FactorPublic HealthRegulator GenesResearchRiskRoleStem Cell FactorSumSurface AntigensSymptomsSystems BiologyTNFRSF1B geneTREM2 geneTechniquesValidationWorkapolipoprotein E-4cell typecohortcytokinedesigndifferential expressiongene networkgene regulatory networkgenetic signaturegenome wide association studygenome-wideinflammatory markerinsightmild cognitive impairmentneuroimagingneuroinflammationnew therapeutic targetnovel therapeutic interventionperipheral bloodpre-clinicalprecision medicinepreventresponsesexsystemic inflammatory responsetherapeutic proteintherapeutic targettherapy developmenttranscriptome sequencingtranscriptomicstranslational study
项目摘要
PROJECT SUMMARY/ABSTRACT
Alzheimer's disease (AD) is the most common cause of dementia worldwide. In the US, it is the fifth leading
cause of death in people over 65 years of age. Delineating factors that predict rate of future cognitive decline
and dementia are important but are yet to be thoroughly understood. Knowledge of disease progression related
biological factors will be critical in designing novel therapeutic strategies to mitigate their deleterious effects and
thereby prevent the associated cognitive and behavioral decline.
The research at the foundation of this R03 is a clinical translational study that uses systems biology and
bioinformatics techniques to characterize the genetic and cellular context of dysregulated inflammatory pathways
in the brain and periphery that impact longitudinal cognitive decline in different stage of Alzheimer's disease. Our
earlier work among clinical patients at the Mild cognitive impairment stage AD suggests that a clinically
meaningful degree of rapid cognitive decline was best predicted by baseline levels of an inflammatory analyte
CCL2. In this work we hope to extend this initial insight by characterizing in depth the genetic drivers behind the
inflammatory deregulation in clinical AD and the cellular context in which it occurs in the periphery and the central
nervous system. We will confirm and validate these changes with genome wide (RNA-seq) expression changes
and against data from other large national data (ADNI, Accelerating Medicines Partnership-AD) and by single
cell transcriptomics of immune cells in the cerebrospinal fluid among well characterized patients. If the hypothesis
and models are validated, scientific insights from this research will help identify novel therapeutic targets and
individual propensities for deleterious inflammatory responses for future precision medicine interventions against
neuroinflammation in AD to prevent disease progression and cognitive decline. If the hypothesis is found to be
not true, the findings from this study will still represent a significant advance in our knowledge of variability in
individual propensities to have a neuroinflammatory response in the face of neurodegenerative disease
pathology. The results of this will be useful both clinically and in designing and interpreting future research
outcomes.
项目总结/文摘
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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Gurkan Bebek其他文献
Gurkan Bebek的其他文献
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{{ truncateString('Gurkan Bebek', 18)}}的其他基金
Integrative analysis of proteomics and transcriptomics to delineate vesicular transport related protein abnormalities related to Alzheimer's, Lewy body and mixed Pathologies
蛋白质组学和转录组学的综合分析,以描述与阿尔茨海默病、路易体和混合病理学相关的囊泡运输相关蛋白质异常
- 批准号:
10444050 - 财政年份:2022
- 资助金额:
$ 16.1万 - 项目类别:
Developing a clinical and research framework for evaluating inflammation pathway dysregulation in Alzheimer's disease
开发评估阿尔茨海默病炎症途径失调的临床和研究框架
- 批准号:
10323668 - 财政年份:2021
- 资助金额:
$ 16.1万 - 项目类别:
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