APOE4 dependent regulation of CSF Complement Pathway Activation in the development of Alzheimer's Disease
APOE4 依赖性调节脑脊液补体通路激活在阿尔茨海默病的发展过程中
基本信息
- 批准号:10871775
- 负责人:
- 金额:$ 40.22万
- 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:2022-07-01 至 2027-02-28
- 项目状态:未结题
- 来源:
- 关键词:AddressAdministrative SupplementAdultAdult ChildrenAgeAge DistributionAgingAliquotAllelesAlzheimer disease preventionAlzheimer&aposs DiseaseAlzheimer&aposs disease riskAmericanAmyloid beta-ProteinAnestheticsApolipoprotein EBacteriaBathingBindingBiological AssayBiologyBrainCaringCarrier ProteinsCell Surface ReceptorsCellsCerebrospinal FluidCheek structureChemicalsCholesterolClinicalCodeComplementComplement ActivationComplexCritiquesDNADataDementiaDevelopmentDiseaseDrug TargetingEatingEducationElderlyEnsureEnvironmental Risk FactorEnzyme-Linked Immunosorbent AssayEuropeFrequenciesGene DosageGenesGeneticGenotypeGoalsHomozygoteHumanImmuneIndianaIndividualInheritedLate Onset Alzheimer DiseaseLife StyleLiquid substanceLongevityMass Spectrum AnalysisMeasuresMemoryMethodsNeurofibrillary TanglesNeuronsOutcomeParentsPathologyPathway interactionsPersonsPopulationProtein SubunitsProteinsProteomicsRaceRegistriesRegulationResearchRiskRoleSample SizeSamplingSenile PlaquesSet proteinSignal TransductionSpainSpinal CordSpinal PunctureSwabSymptomsSynapsesThinkingUnited States National Institutes of HealthUniversitiesWashingtonWisconsinWorkagedapolipoprotein E-3apolipoprotein E-4biobankcohortcomplement pathwaygenetic risk factorgenetic variantneuropathologypreventrecruitrepositorysexskillstau Proteinstau-1traitvirtualyoung adult
项目摘要
Dementia is a common disorder that increases in frequency in the elderly. Dementia is a
progressive loss of thinking and memory skills that eventually results in an inability to care for
oneself and to live independently. The most common cause of dementia in older Americans is
Alzheimer’s Disease, which develops as a result of multiple lifestyle/environmental factors and
inherited or familial causes. Many familial traits (such as the risk of developing Alzheimer’s
disease) are inherited genetically, through gene variants (sequences of a chemical code called
DNA). The most common genetic variant that increases the risk of Alzheimer’s disease is called
APOE4. Although we have known for over 25 years that inheriting an APOE4 genetic variant (also
called an allele) increases Alzheimer’s disease risk, it is unclear how and why APOE4 increases
this risk. Recent data has raised the possibility that APOE4 may act by increasing the activation
of the complement pathway, a set of proteins that are used by immune cells to kill and eat bacteria,
and that also play a role in “killing” and “eating” connections between nerve cells in the brain,
known as synapses. In this project, we will examine whether people that carry the APOE4 allele
(either 1 or 2 copies of this allele) have increased evidence of complement pathway activation in
the fluid that bathes their brain and spinal cord, known as the cerebrospinal fluid (CSF) across
the full adult lifespan. We have begun to assemble a set of CSF samples from our own studies
as well as biobanks in the US and Europe. To date we have collected or received approval to
use CSF samples from 400 individuals. This administrative supplement will allow us to recruit
additional subjects between the ages of 18-39 to complete the set of CSF samples needed for
this analysis. These samples will be analyzed using an advanced method that can measure the
levels of a large percentage of all proteins present in human CSF, and which can precisely
measure the levels of proteins in the complement pathway. Overall, this work will help us
understand how and why APOE4 changes the function of the brain, and how and why it
contributes to AD risk. This work is an early step towards identifying proteins or pathways that
could be targeted by drugs to prevent Alzheimer’s disease in people that carry an APOE4 allele
before the onset of any clinical symptoms.
痴呆症是一种常见的疾病,在老年人中发病率增加。痴呆症是一种
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Miles Berger其他文献
Miles Berger的其他文献
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{{ truncateString('Miles Berger', 18)}}的其他基金
APOE4 dependent regulation of CSF Complement Pathway Activation in the development of Alzheimer's Disease
APOE4 依赖性调节脑脊液补体通路激活在阿尔茨海默病的发展过程中
- 批准号:
10650372 - 财政年份:2022
- 资助金额:
$ 40.22万 - 项目类别:
Low Neurophysiologic Resistance to Anesthetics as a Marker of Preclinical/Prodromal Alzheimer's Disease and Neurovascular Pathology, Delirium risk and Inattention
对麻醉药的神经生理学抵抗力低是临床前/前驱阿尔茨海默病和神经血管病理学、谵妄风险和注意力不集中的标志
- 批准号:
10870632 - 财政年份:2022
- 资助金额:
$ 40.22万 - 项目类别:
Low Neurophysiologic Resistance to Anesthetics as a Marker of Preclinical/Prodromal Alzheimer's Disease and Neurovascular Pathology, Delirium risk and Inattention
对麻醉药的神经生理学抵抗力低是临床前/前驱阿尔茨海默病和神经血管病理学、谵妄风险和注意力不集中的标志
- 批准号:
10671023 - 财政年份:2022
- 资助金额:
$ 40.22万 - 项目类别:
Low Neurophysiologic Resistance to Anesthetics as a Marker of Preclinical/Prodromal Alzheimer's Disease and Neurovascular Pathology, Delirium risk and Inattention
对麻醉药的神经生理学抵抗力低是临床前/前驱阿尔茨海默病和神经血管病理学、谵妄风险和注意力不集中的标志
- 批准号:
10521860 - 财政年份:2022
- 资助金额:
$ 40.22万 - 项目类别:
Neuro-inflammation in Postoperative Cognitive Dysfunction: CSF and fMRI Studies
术后认知功能障碍中的神经炎症:脑脊液和功能磁共振成像研究
- 批准号:
9390592 - 财政年份:2017
- 资助金额:
$ 40.22万 - 项目类别:
Neuro-inflammation in Postoperative Cognitive Dysfunction: CSF and fMRI Studies
术后认知功能障碍中的神经炎症:脑脊液和功能磁共振成像研究
- 批准号:
10598925 - 财政年份:2017
- 资助金额:
$ 40.22万 - 项目类别:
Neuro-inflammation in Postoperative Cognitive Dysfunction: CSF and fMRI Studies
术后认知功能障碍中的神经炎症:脑脊液和功能磁共振成像研究
- 批准号:
9898206 - 财政年份:2017
- 资助金额:
$ 40.22万 - 项目类别:
Neuro-inflammation in Postoperative Cognitive Dysfunction: CSF and fMRI Studies
术后认知功能障碍中的神经炎症:脑脊液和功能磁共振成像研究
- 批准号:
10160751 - 财政年份:2017
- 资助金额:
$ 40.22万 - 项目类别:
The Significance of Perioperative Changes in CSF tau levels in the Elderly
老年人围手术期脑脊液 tau 水平变化的意义
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9123506 - 财政年份:2015
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Role of 5-HT1A-AR overexpression in affective disorders
5-HT1A-AR 过表达在情感障碍中的作用
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7281976 - 财政年份:2005
- 资助金额:
$ 40.22万 - 项目类别:
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