Protein Signatures of APOE2 and Cognitive Aging
APOE2 的蛋白质特征和认知衰老
基本信息
- 批准号:10219143
- 负责人:
- 金额:$ 64.14万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-30 至 2023-05-31
- 项目状态:已结题
- 来源:
- 关键词:AgeAgingAllelesAlzheimer&aposs DiseaseApolipoprotein EBiologicalBiological AssayBiological MarkersBlood specimenBostonCardiovascular systemCentenarianCognitive agingCollaborationsDataData AnalysesData SetDementiaDiseaseEarly DiagnosisEnrollmentEthnic OriginEvaluationEventFrequenciesFundingGenesGenotypeHumanImpaired cognitionInflammationInterventionLate Onset Alzheimer DiseaseLinkLongevityMeasuresModelingMolecularMonitorNeurodegenerative DisordersNew EnglandNonesterified Fatty AcidsParticipantPatternPlasmaPlasma ProteinsPost-Translational Protein ProcessingPrevalenceProteinsProteomicsPublic HealthResearchResearch PersonnelRisk FactorsRoleSNP genotypingSamplingSet proteinStructureSubjects SelectionsTechnologyTestingTherapeuticTranslatingUnited States National Institutes of HealthUniversitiesValidationWorkaging populationcognitive changecognitive functioncohortcostearly detection biomarkershealthy aginginflammatory markerinsightlipid metabolismoffspringpredictive signaturepreservationpreventprotective alleleprotein biomarkersrate of changescreeningsocioeconomicstherapeutic target
项目摘要
Abstract
Apolipoprotein E is a class of proteins involved in lipid metabolism with functions determined by
alleles of the gene APOE. The least common allele of this gene, called 𝑒2, emerged as a putative
protective variant when Schachter et al. noted an increased frequency of 𝑒2 in French
centenarians. Since then several studies have provided evidence that 𝑒2 has a beneficial neuroprotective
effect and promotes longevity and healthy aging. The New England Centenarian Study (NECS) directed
by Dr. Perls has enrolled ~400 𝑒2 carriers since 1994,
and in collaboration with the Longenity Study (LS) directed by Dr. Barzilai and other studies of
centenarians produced strong evidence that 𝑒2promotes longevity. Despite multiple research
efforts however the biological mechanisms associated with 𝑒2 are still unclear. We generated in
collaboration with Novartis a proteomic dataset of ~5,000 proteins from sera of 226 NECS
participants, ages 50 to 115 years, selected to be enriched
of 𝑒2 and we analyzed these data in the context of APOE genotypes. In our analysis, we
discovered a preliminary set of proteins that correlate with APOE genotypes and predict different
longitudinal patterns of cognitive decline. These preliminary data support the hypothesis that
there are multiple plasma proteins associated with APOE genotypes that (i) can be used to predict
cognitive decline or preservation better than APOE genotypes, and (ii) can inform us about
potential mechanisms of action of APOE and suggest candidate interventions to prevent or delay
neurodegenerative diseases and cognitive decline in aging. We propose to test this hypothesis in
three ways: we will use in-depth proteomics to validate, characterize and expand the set of
proteins that correlate with APOE genotypes in plasma of 50 carriers of different APOE genotypes.
This analysis will likely discover additional protein biomarkers associated with APOE genotypes as
well as post- translational modifications that could modify their molecular functions. We will then
evaluate the effect of the expanded protein signature on aging and cognitive decline in 600
centenarians, their offspring and controls from the NECS, and replicate findings with the LS. In a
subset of these subjects, we will assay protein levels in a second blood sample collected few years
apart to be able to examine how changes of the protein signature predict changes of cognitive
functions. We also propose to augment these data with selected markers of inflammation and free
fatty acids that are important factors in cognitive aging and conduct integrative analyses of the
data collected in the various aims to model hypothetical mechanisms linking APOE genotypes to
cognitive aging. In summary, we have assembled a competent, interdisciplinary team of investigators
to thoroughly evaluate and characterize protein signatures of APOE genotypes that could become
multipurpose, potent biomarkers of cognitive functions change and probable AD. The results of this
work will suggest possible mechanisms that determine the neuroprotective effect of the APOE 𝑒2 allele.
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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THOMAS T PERLS其他文献
THOMAS T PERLS的其他文献
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{{ truncateString('THOMAS T PERLS', 18)}}的其他基金
Identifying protective omics profiles in centenarians and translating these into preventive and therapeutic strategies
确定百岁老人的保护性组学特征并将其转化为预防和治疗策略
- 批准号:
10017131 - 财政年份:2019
- 资助金额:
$ 64.14万 - 项目类别:
Identifying protective omics profiles in centenarians and translating these into preventive and therapeutic strategies
确定百岁老人的保护性组学特征并将其转化为预防和治疗策略
- 批准号:
10678171 - 财政年份:2019
- 资助金额:
$ 64.14万 - 项目类别:
Identifying protective omics profiles in centenarians and translating these into preventive and therapeutic strategies
确定百岁老人的保护性组学特征并将其转化为预防和治疗策略
- 批准号:
10449626 - 财政年份:2019
- 资助金额:
$ 64.14万 - 项目类别:
Protein Signatures of APOE2 and Cognitive Aging
APOE2 的蛋白质特征和认知衰老
- 批准号:
10451539 - 财政年份:2018
- 资助金额:
$ 64.14万 - 项目类别:
Protein Signatures of APOE2 and Cognitive Aging
APOE2 的蛋白质特征和认知衰老
- 批准号:
10408304 - 财政年份:2018
- 资助金额:
$ 64.14万 - 项目类别:
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