Impact of TBI and Cognitive Decline on Alzheimer's Disease Brain-Derived Exosome Cargo
TBI 和认知能力下降对阿尔茨海默病脑源性外泌体货物的影响
基本信息
- 批准号:10662883
- 负责人:
- 金额:$ 194.82万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-06-01 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAddressAgeAge-associated memory impairmentAgingAlzheimer disease detectionAlzheimer&aposs DiseaseAlzheimer&aposs disease brainAlzheimer&aposs disease riskAlzheimer’s disease biomarkerAmyloid beta-ProteinAstrocytesAttentionAwardBiological AssayBiological MarkersBloodBrainCellsCerebrospinal FluidChronicClinical TrialsCognitionCognitiveComplementCytoskeletonDataDiagnosisDiseaseDizygotic TwinsEligibility DeterminationEndosomesGeneticGenotypeHeritabilityImpaired cognitionIndividualInflammatoryInjuryLiquid substanceLongitudinal cohort studyMagnetic Resonance ImagingMembraneMolecularMonozygotic twinsNatureNerve DegenerationNeurodegenerative DisordersNeuronal DysfunctionNeuronal InjuryNeuronsPathologicPathologyPathway interactionsPeripheralPhasePlasmaPlasma ProteinsPost-Traumatic Stress DisordersProteinsProteomicsRecording of previous eventsRiskSamplingSurfaceSynapsesTestingTraumatic Brain InjuryTwin Multiple BirthTwin StudiesVariantVesicleVeteransVietnamagedapolipoprotein E-4biobankbiomarker identificationbiomarker performancecell typecognitive changecohortcomorbiditycytokineexosomeexperiencehuman old age (65+)mental functionmiddle ageneurograninneuroimagingneuropathologynovelpersistent symptomphenotypic dataspecific biomarkerstau Proteinstau-1tooltreatment trialvesicular release
项目摘要
PROJECT SUMMARY ABSTRACT
Exosomes remove proteins and cellular substituents, and also shuttle protein cargo between cells and also to
the periphery. Unlike freely circulating proteins, exosomes are identified by surface markers that include
designations of cell type origin. Astrocyte and neuronally-derived exosomes (ADEs and NDEs, respectively)
from plasma are identified by specific membrane markers, providing an accessible substrate to identify
biomarkers and mechanisms of neuropathology. The potential for NDEs to identify TBI-related biomarkers
however is just beginning to be explored.
Our lab has a large focus on exosome biomarkers in TBI and neurodegeneration. Our data demonstrate
that Alzheimer's disease (AD) neuropathological proteins, amyloid-beta and phospho-tau are sequestered in
NDEs and are more sensitive biomarkers of AD than free proteins in native plasma. In terms of Veterans with
TBI, we and others have found that NDEs have increased levels of Aβ, proteins associated with neuronal injury
and synaptic proteins. We have also shown that complement protein cargo in ADEs is also associated with
AD. Although exciting, these studies represent relatively small studies in samples from younger individuals
with limited information about the relationship between exosome protein cargo and functional changes. To
examine CNS-enriched exosome proteins as biomarkers of TBI and associated cognitive decline in older
individuals, we will leverage banked plasma samples from the Vietnam Era Twin Study of Aging (VETSA), a
longitudinal cohort study of US Veterans who had a mean age of 56 at the first assessment wave and 67 at the
most recently completed third assessment. In this Merit Award proposal we propose to determine the utility of
neurodegenerative disease proteins within NDEs as biomarkers to predict cognitive change in aging twin
Veterans with post-traumatic stress disorder and TBI and also to identify the mechanisms underlying the
relationship between inflammatory pathways, cognition and neurodegeneration associated with TBI and PTSD
in VETSA. Our overarching hypothesis is that remote TBI is associated with abnormalities in cytoskeletal and
neuronal proteins in circulating NDEs. We also hypothesize that remote TBI causes chronic changes in central
inflammatory tone which leads to abnormalities in complement and cytokine proteins in circulating ADEs
项目摘要
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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Victoria B Risbrough其他文献
Victoria B Risbrough的其他文献
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{{ truncateString('Victoria B Risbrough', 18)}}的其他基金
Validation of PTSD signals across multiple biological domains for the development of diagnostic biomarkers for PTSD in military populations to improve clinical care of Veterans
跨多个生物领域验证 PTSD 信号,以开发军人群体中 PTSD 的诊断生物标志物,从而改善退伍军人的临床护理
- 批准号:
10617231 - 财政年份:2022
- 资助金额:
$ 194.82万 - 项目类别:
Validation of PTSD signals across multiple biological domains for the development of diagnostic biomarkers for PTSD in military populations to improve clinical care of Veterans
跨多个生物领域验证 PTSD 信号,以开发军人群体中 PTSD 的诊断生物标志物,从而改善退伍军人的临床护理
- 批准号:
10365835 - 财政年份:2022
- 资助金额:
$ 194.82万 - 项目类别:
BLRD Research Career Scientist Award Application
BLRD 研究职业科学家奖申请
- 批准号:
10588850 - 财政年份:2022
- 资助金额:
$ 194.82万 - 项目类别:
Neuronal exosomes to identify biomarkers and pathology of deployment-related TBI
神经元外泌体识别部署相关 TBI 的生物标志物和病理学
- 批准号:
10292911 - 财政年份:2018
- 资助金额:
$ 194.82万 - 项目类别:
Neuronal exosomes to identify biomarkers and pathology of deployment-related TBI
神经元外泌体识别部署相关 TBI 的生物标志物和病理学
- 批准号:
10046280 - 财政年份:2018
- 资助金额:
$ 194.82万 - 项目类别:
Neuronal exosomes to identify biomarkers and pathology of deployment-related TBI
神经元外泌体识别部署相关 TBI 的生物标志物和病理学
- 批准号:
9561543 - 财政年份:2018
- 资助金额:
$ 194.82万 - 项目类别:
Role of COMTval158met in PTSD risk and treatment response
COMTval158met 在 PTSD 风险和治疗反应中的作用
- 批准号:
8730388 - 财政年份:2014
- 资助金额:
$ 194.82万 - 项目类别:
Role of COMTval158met in PTSD risk and treatment response
COMTval158met 在 PTSD 风险和治疗反应中的作用
- 批准号:
8967100 - 财政年份:2014
- 资助金额:
$ 194.82万 - 项目类别:
Fragmented early-life experiences, aberrant circuit maturation, emotional vulnerabilities
破碎的早期生活经历、异常的电路成熟、情感脆弱
- 批准号:
10595601 - 财政年份:2013
- 资助金额:
$ 194.82万 - 项目类别:
Fragmented early-life experiences, aberrant circuit maturation, emotional vulnerabilities
破碎的早期生活经历、异常的电路成熟、情感脆弱
- 批准号:
10379271 - 财政年份:2013
- 资助金额:
$ 194.82万 - 项目类别:
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