ncRNAs in plasma EVs of AD patients and their discriminatory power as biomarkers
AD 患者血浆 EV 中的 ncRNA 及其作为生物标志物的区分能力
基本信息
- 批准号:10532000
- 负责人:
- 金额:$ 229.75万
- 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:2022-09-15 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:14q32AffectAgreementAllelesAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAmyloidAmyloid beta-42Amyloid beta-ProteinArea Under CurveAutopsyBindingBiogenesisBiological AssayBiological MarkersBloodBrainCerebrospinal FluidClinicData SetDementiaDiagnosisDiagnosticDiagnostic testsDiseaseDisease ProgressionEarly DiagnosisEpigenetic ProcessFamilyGenesGenetic TranscriptionGenomicsGenotypeGoalsHumanHuman ActivitiesImaging technologyMagnetic Resonance ImagingMeasuresMediatingMessenger RNAMethylationModelingMolecularMonitorMusNatureNeuronsPathologicPatientsPatternPerformancePhenotypePlasmaPopulationPositron-Emission TomographyPredispositionPropertyProtein IsoformsProteinsResearchRiskSNRPNSamplingSmall Nucleolar RNAStandardizationTechnologyTestingTherapeutic EffectTranscriptUBE3A geneUntranslated RNAValidationamyloid imagingbasecohortcostdetection sensitivitydiagnostic accuracydiagnostic strategyepigenomicsextracellular vesicleshyperphosphorylated tauimprintmachine learning algorithmmind controlmouse modelneuroimaging markernon-dementedpreventpromoterprospectiveprotective effectsample collectiontau Proteinstau aggregationtau-1
项目摘要
Alzheimer's disease is the most common and economically impactful form of dementia.
Approaches based on cerebrospinal fluid and blood have been established to measure the levels
of amyloid beta and hyperphosphorylated tau to facilitate early diagnosis of AD or to monitor the
effects of therapeutics and progression of the disease. Plasma extracellular vesicles (EVs) and
their cargo present an opportunity to isolate and profile molecules associated with human
pathological conditions. We have recently discovered small nucleolar non-coding RNAs
(snoRNAs) highly enriched in plasma EVs of AD patients compared to non-demented controls.
We posit that tau aggregates irreversibly bind snoRNAs preventing them from performing their
normal function resulting in a compensatory increase of their expression in AD brains. Our
hypothesis is that the expression of certain SNORDs and their secretion in neuron derived EVs is
increased with the progression of AD. Small non-coding nucleolar snoRNAs might represent ideal
biomarkers, compared with proteins and/or mRNAs, because of the protective effect of plasma
EV and the unprecedented sensitivity of detection by ddPCR technology – down to single
transcripts.
This proposal's primary goals are: 1) to test and validate the diagnostic accuracy of SNORD115
and SNORD116 ddPCR assays in human plasma; 2) to understand the nature of the associations
between the abundance of particular SNORDs in AD plasma EVs, their expression level in brain,
the disease state and progression, and if there is an association with APOE genotype; 3) to test
for epigenetic mechanisms underlying the changes in abundance of SNORDs, and 4) using AD
mouse models to reveal the effect of amyloid and tau aggregation on ISF, CSF and plasma EVs
cargo. A better understanding of the underlying regulatory genomic, epigenomic, and cellular
mechanisms responsible for the differences in the enrichment of SNORDs in plasma EVs of AD
patients compared to Controls would help understand essential aspects of APOE mediated risk
of AD and in establishing reliable diagnostic strategies.
阿尔茨海默病是最常见和经济上最具影响力的痴呆症形式。
已经建立了基于脑脊液和血液的方法来测量水平
淀粉样蛋白β和过度磷酸化的tau蛋白,以促进AD的早期诊断或监测
治疗效果和疾病进展。血浆细胞外囊泡(EV)和
他们的货物提供了一个机会,分离和分析与人类相关的分子,
病理条件。我们最近发现了小的核仁非编码RNA
与非痴呆对照相比,在AD患者的血浆EV中高度富集的RNA(snoRNA)。
我们认为,tau聚集体不可逆地结合snoRNA,阻止它们执行其功能。
正常功能,导致其在AD脑中表达的代偿性增加。我们
一种假设是,某些SNORD的表达及其在神经元衍生的EV中的分泌是
随着AD的进展而增加。小的非编码核仁snoRNA可能代表理想的
与蛋白质和/或mRNA相比,由于血浆的保护作用,
EV和ddPCR技术前所未有的检测灵敏度-低至单个
成绩单
该方案的主要目标是:1)测试和验证SNORD 115的诊断准确性
和SNORD 116 ddPCR检测; 2)了解相关性的性质
AD血浆EV中特定SNORD的丰度,它们在脑中的表达水平,
疾病状态和进展,以及是否与APOE基因型相关; 3)检测
SNORD丰度变化的表观遗传机制,以及4)使用AD
揭示淀粉样蛋白和tau聚集对ISF、CSF和血浆EV的影响的小鼠模型
货物.更好地了解潜在的调控基因组,表观基因组和细胞
负责AD血浆EV中SNORD富集差异的机制
与对照组相比,患者将有助于了解APOE介导风险的基本方面
以及建立可靠的诊断策略。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
RADOSVETA KOLDAMOVA其他文献
RADOSVETA KOLDAMOVA的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('RADOSVETA KOLDAMOVA', 18)}}的其他基金
The interplay between Tau and ncRNAs – genomic and epigenomic clues to early AD pathogenesis
Tau 和 ncRNA 之间的相互作用 — 早期 AD 发病机制的基因组和表观基因组线索
- 批准号:
10447273 - 财政年份:2022
- 资助金额:
$ 229.75万 - 项目类别:
The interplay between Tau and ncRNAs – genomic and epigenomic clues to early AD pathogenesis
Tau 和 ncRNA 之间的相互作用 — 早期 AD 发病机制的基因组和表观基因组线索
- 批准号:
10634661 - 财政年份:2022
- 资助金额:
$ 229.75万 - 项目类别:
APOE Orchestrated Molecular Signatures in Aging Brain and AD-the Contribution of APOE2
APOE 在衰老大脑和 AD 中精心设计的分子特征——APOE2 的贡献
- 批准号:
10450775 - 财政年份:2018
- 资助金额:
$ 229.75万 - 项目类别:
APOE Orchestrated Molecular Signatures in Aging Brain and AD-the Contribution of APOE2
APOE 在衰老大脑和 AD 中精心设计的分子特征——APOE2 的贡献
- 批准号:
10170188 - 财政年份:2018
- 资助金额:
$ 229.75万 - 项目类别:
APOE orchestrated ''molecular signatures'' in aging brain and AD - the contribution of APOE2
APOE 在衰老大脑和 AD 中精心策划了“分子特征”——APOE2 的贡献
- 批准号:
9555298 - 财政年份:2017
- 资助金额:
$ 229.75万 - 项目类别:
Epigenetic and phenotypic effects of arsenic: impacts on cognition and AD
砷的表观遗传和表型效应:对认知和 AD 的影响
- 批准号:
8755745 - 财政年份:2014
- 资助金额:
$ 229.75万 - 项目类别:
LXR and human ApoE isoform effects on AD phenotype: in vitro and in vivo models
LXR 和人 ApoE 亚型对 AD 表型的影响:体外和体内模型
- 批准号:
8103681 - 财政年份:2011
- 资助金额:
$ 229.75万 - 项目类别:
LXR and human ApoE isoform effects on AD phenotype: in vitro and in vivo models
LXR 和人 ApoE 亚型对 AD 表型的影响:体外和体内模型
- 批准号:
8484324 - 财政年份:2011
- 资助金额:
$ 229.75万 - 项目类别:
LXR and human ApoE isoform effects on AD phenotype: in vitro and in vivo models
LXR 和人 ApoE 亚型对 AD 表型的影响:体外和体内模型
- 批准号:
8277207 - 财政年份:2011
- 资助金额:
$ 229.75万 - 项目类别:
LXR and human ApoE isoform effects on AD phenotype: in vitro and in vivo models
LXR 和人 ApoE 亚型对 AD 表型的影响:体外和体内模型
- 批准号:
8665344 - 财政年份:2011
- 资助金额:
$ 229.75万 - 项目类别:
相似海外基金
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 229.75万 - 项目类别:
Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 229.75万 - 项目类别:
Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 229.75万 - 项目类别:
Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 229.75万 - 项目类别:
Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 229.75万 - 项目类别:
Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 229.75万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 229.75万 - 项目类别:
Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
- 批准号:
2301846 - 财政年份:2023
- 资助金额:
$ 229.75万 - 项目类别:
Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 229.75万 - 项目类别:
Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
- 批准号:
23K16076 - 财政年份:2023
- 资助金额:
$ 229.75万 - 项目类别:
Grant-in-Aid for Early-Career Scientists