Development of in vivo quantitative stable isotope probing to quantify microbiome dynamics in Alzheimers Disease
开发体内定量稳定同位素探测以量化阿尔茨海默病微生物组动态
基本信息
- 批准号:10473765
- 负责人:
- 金额:$ 19万
- 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:2021-09-01 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:16S ribosomal RNA sequencing3xTg-AD mouseAD transgenic miceAddressAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAlzheimer&aposs disease pathologyAlzheimer&aposs disease riskAmyloidAmyloid beta-ProteinAmyloidosisBacteriaBlood - brain barrier anatomyBrainCardiovascular systemCessation of lifeCommunitiesDNADNA sequencingDataDeath RateDementiaDensity Gradient CentrifugationDepositionDevelopmentDisease ProgressionEcologyEcosystemElderlyEnteric Nervous SystemEtiologyExhibitsGastrointestinal tract structureGoalsGrowthHealthHumanHuman MicrobiomeHuman bodyImmuneImmune systemIndividualInflammatoryIsotope LabelingIsotopesLabelLongitudinal StudiesMeasuresMethodsMicrobeMouse StrainsMusNatureNerve DegenerationNeurofibrillary TanglesNeurologicNeurotransmittersNucleic AcidsPathogenesisPathologicPathologyPatientsPhase III Clinical TrialsPopulationPopulation DynamicsProcessProductionProteinsQuality of lifeRNAResearchResearch PersonnelRoleSenile PlaquesSeveritiesShotgunsSoilStructureTauopathiesTaxonTechniquesTechnologyTimeTransgenic OrganismsVagus nerve structureVolatile Fatty AcidsWaterWild Type Mouseabeta accumulationaging populationbasebeta pleated sheetblood-brain barrier crossingcognitive functiondensitydisorder preventiondisorder riskgut microbiomegut microbiotagut-brain axishost microbiomehost-associated microbial communitieshuman diseasehuman microbiotain vivoinnovationinsightinterestmembermetagenomic sequencingmicrobialmicrobial communitymicrobial hostmicrobiomemicrobiome compositionmicrobiome researchmicrobiome sequencingmicrobiotamicroorganismmouse modelneuroinflammationneuropathologynew technologynovelpathogenic microbestable isotopetoolvagus nerve stimulationβ-amyloid burden
项目摘要
ABSTRACT
Alzheimer’s Disease (AD) is the leading cause of dementia in the aging population and severely
impacts patient’s and caretaker’s quality of life. Despite decades of research, the underlying etiology of
AD is incompletely understood. The prevailing hypothesis for AD pathology is the amyloid cascade
hypothesis, which posits that the causative agent of AD is the accumulation of amyloid-β (Aβ, the main
component of plaques) in the brain. However, recent Phase III clinical trials that target Aβ have not led
to significant improvements in cognitive function, despite reducing overall brain Aβ burden. There has
been a growing interest in understanding additional pathological features of AD that may impact
disease progression. Recent studies in humans and in mice have suggested a role for pathogenic
microbes or altered microbiota in neuroinflammation and AD. Microbiota in the GI tract can influence
neurological health through microbial production of neurotransmitter precursors, immune-modulatory
metabolites (e.g. short chain fatty acids), or interaction with the vagus nerve or enteric nervous system.
Gut microbiota can also produce amyloids (aggregated, insoluble proteins exhibiting β-pleated sheet
structures) that may cross the blood-brain barrier. Despite growing efforts to understand the gut
microbiome-brain axis, current technologies using DNA or RNA amplicon sequencing are unable to
address fundamental ecological questions, such as quantifying taxon-specific growth rates of host-
associated microbiota. Understanding microbial ecosystem dynamics has large implications for human
disease; quantifying growth or turnover of species in terms of absolute abundance change over time in
an ecosystem can enable predictions of interspecies competition or trajectories of microbial succession
in early and late life, which are associated with host health or disease risk. In this study, we will adapt
an innovative technique widely used in soil microbial ecology to study host-microbiome dynamics in AD.
We will use quantitative stable isotope probing (qSIP), a technique that uses an isotopically enriched
substrate (e.g. 18O-water) to measure gut microbiome dynamics in triple transgenic (3xTg-AD) and wild-
type mice. Since H2O is a universal substrate, labeled 18O will incorporate into microbial and host
biomolecules, including nucleic acids; this feature allows a researcher to separate extracted DNA by
density to quantify taxon-specific growth rates. Completion of this study will lead to the development of
a novel tool that can be widely used in the AD community to better understand the contribution of host-
associated microbiota to AD progression and neuroinflammation.
摘要
项目成果
期刊论文数量(0)
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Emily K Cope其他文献
Emily K Cope的其他文献
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{{ truncateString('Emily K Cope', 18)}}的其他基金
Development of in vivo quantitative stable isotope probing to quantify microbiome dynamics in Alzheimers Disease
开发体内定量稳定同位素探测以量化阿尔茨海默病微生物组动态
- 批准号:
10301904 - 财政年份:2021
- 资助金额:
$ 19万 - 项目类别:
Evaluation of Soluble Fiber as a Strategy to Decrease Asthma Morbidity in Underserved Populations
可溶性纤维作为降低服务不足人群哮喘发病率策略的评估
- 批准号:
10707490 - 财政年份:2017
- 资助金额:
$ 19万 - 项目类别:
Evaluation of Soluble Fiber as a Strategy to Decrease Asthma Morbidity in Underserved Populations
可溶性纤维作为降低服务不足人群哮喘发病率策略的评估
- 批准号:
10555413 - 财政年份:2017
- 资助金额:
$ 19万 - 项目类别:
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