Integrative translational discovery of vascular risk factors in aging and dementia

衰老和痴呆血管危险因素的综合转化发现

基本信息

  • 批准号:
    9421402
  • 负责人:
  • 金额:
    $ 357.77万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-15 至 2020-05-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Alzheimer's disease (AD) is the most common cause of dementia characterized by brain accumulation of senile plaques and neurofibrillary tangles. AD risk is likely influenced by a multitude of genetic and environmental risk factors and their complex interplay, which subsequently lead to cascades of downstream pathophysiologic events that include but are not limited to aberrant proteostasis and lipid metabolism, as well as inflammatory, vascular, and oxidative mechanisms. The array of risk factors that lead to AD and their downstream influences are likely to be heterogeneous amongst AD patients, which complicates the search for drug targets, biomarkers and their potential downstream beneficial use in any given AD patient. For this reason, drug target and biomarker discovery efforts in AD have to focus on identification of both molecular mechanisms that are commonly perturbed in AD patients, as well as those mechanisms that may underlie heterogeneity in AD. To overcome this massive challenge, team-science efforts, including the NIH initiatives, Accelerating Medicines Partnership-AD (AMP-AD) and Molecular Mechanisms of the Vascular Etiology of AD (M2OVE-AD) Consortia, have launched large-scale generation and analyses of multi-omics data from well- phenotyped human cohorts and model systems. These consortia aim to integrate multi-omics and clinical endophenotype data to build a model(s) of AD that captures these common and heterogeneous pathomechanisms. Our teams are leading participants of both AMP-AD and M2OVE-AD. The initial findings from these consortia reveal concerted changes in networks of expressed genes and proteins in AD subjects and model systems, with biological significance. Despite this progress and wide and immediate sharing of the data generated by these programs, significant gaps remain in the available –omics data, and the ability to integrate, harmonize and annotate these datasets. Our proposal is in response to the RFA-AG-17-054, which aims to close these gaps. In this proposal, we maintain the overall objective of our parent funded M2OVE-AD project (RF1 AG51504), which is to determine APOE- and sex-dependent effects, and uncover novel genes and pathways that influence vascular risk in aging, AD and other dementias. Our specific aims are: 1. Integrative functional genomic analysis of human brains to discover novel pathways in AD. 2. Integrative functional genomic analysis in a prospective cohort to validate and discover AD pathways. 3. Investigate the impact of APOE genotype and sex on transcriptional networks and the metabolome in model systems. 4. Perform single-cell profiling to annotate the transcriptome data from AMP-AD and M2OVE-AD. These studies will add key epigenetic data (H3K9Ac and RRBS methylome) to the human and transcriptome and metabolomics data to the mouse cohorts, generate human and mouse single cell transcriptome data, and perform integrative network analyses. We expect this proposal to fill key gaps in knowledge and further enhance the AMP-AD and M2OVE-AD initiatives in their drug and biomarker discovery goals.
项目总结/文摘

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 }}

GUOJUN BU其他文献

GUOJUN BU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('GUOJUN BU', 18)}}的其他基金

TREM2-mediated microglial dynamic function in Alzheimer disease
TREM2 介导的阿尔茨海默病小胶质细胞动态功能
  • 批准号:
    9914464
  • 财政年份:
    2020
  • 资助金额:
    $ 357.77万
  • 项目类别:
TREM2-mediated microglial dynamic function in Alzheimer disease
TREM2 介导的阿尔茨海默病小胶质细胞动态功能
  • 批准号:
    10088365
  • 财政年份:
    2020
  • 资助金额:
    $ 357.77万
  • 项目类别:
Integrative translational discovery of vascular risk factors in aging and dementia
衰老和痴呆血管危险因素的综合转化发现
  • 批准号:
    9001610
  • 财政年份:
    2015
  • 资助金额:
    $ 357.77万
  • 项目类别:
ApoE isoform-specific therapy for Alzheimer disease
ApoE 异构体特异性治疗阿尔茨海默病
  • 批准号:
    8744260
  • 财政年份:
    2013
  • 资助金额:
    $ 357.77万
  • 项目类别:
ApoE isoform-specific therapy for Alzheimer disease
ApoE 异构体特异性治疗阿尔茨海默病
  • 批准号:
    9104070
  • 财政年份:
    2013
  • 资助金额:
    $ 357.77万
  • 项目类别:
ApoE isoform-specific therapy for Alzheimer disease
ApoE 异构体特异性治疗阿尔茨海默病
  • 批准号:
    9291405
  • 财政年份:
    2013
  • 资助金额:
    $ 357.77万
  • 项目类别:
ApoE isoform-specific therapy for Alzheimer disease
ApoE 异构体特异性治疗阿尔茨海默病
  • 批准号:
    8894356
  • 财政年份:
    2013
  • 资助金额:
    $ 357.77万
  • 项目类别:
ApoE isoform-specific therapy for Alzheimer disease
ApoE 异构体特异性治疗阿尔茨海默病
  • 批准号:
    8608893
  • 财政年份:
    2013
  • 资助金额:
    $ 357.77万
  • 项目类别:
BRAIN LIPID METABOLISM, DENDRITES AND SYNAPSES IN AGING AND ALZHEIMER'S DISEASE
衰老和阿尔茨海默病中的脑脂质代谢、树突和突触
  • 批准号:
    8183828
  • 财政年份:
    2010
  • 资助金额:
    $ 357.77万
  • 项目类别:
BRAIN LIPID METABOLISM, DENDRITES AND SYNAPSES IN AGING AND ALZHEIMER'S DISEASE
衰老和阿尔茨海默病中的脑脂质代谢、树突和突触
  • 批准号:
    8721290
  • 财政年份:
    2010
  • 资助金额:
    $ 357.77万
  • 项目类别:

相似国自然基金

靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
  • 批准号:
    JCZRQN202500010
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
  • 批准号:
    2025JJ70209
  • 批准年份:
    2025
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
  • 批准号:
  • 批准年份:
    2024
  • 资助金额:
    0 万元
  • 项目类别:
    面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
  • 批准号:
    2023JJ50274
  • 批准年份:
    2023
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
  • 批准号:
  • 批准年份:
    2022
  • 资助金额:
    33 万元
  • 项目类别:
    地区科学基金项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
  • 批准号:
    n/a
  • 批准年份:
    2022
  • 资助金额:
    10.0 万元
  • 项目类别:
    省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
  • 批准号:
    81973577
  • 批准年份:
    2019
  • 资助金额:
    55.0 万元
  • 项目类别:
    面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
  • 批准号:
    81602908
  • 批准年份:
    2016
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
  • 批准号:
    81501928
  • 批准年份:
    2015
  • 资助金额:
    18.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

The Phenomenon of Stem Cell Aging according to Methylation Estimates of Age After Hematopoietic Stem Cell Transplantation
根据造血干细胞移植后甲基化年龄估算干细胞衰老现象
  • 批准号:
    23K07844
  • 财政年份:
    2023
  • 资助金额:
    $ 357.77万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Analysis of Age-dependent Functional Changes in Skeletal Muscle CB1 Receptors by an in Vitro Model of Aging-related Muscle Atrophy
通过衰老相关性肌肉萎缩的体外模型分析骨骼肌 CB1 受体的年龄依赖性功能变化
  • 批准号:
    22KJ2960
  • 财政年份:
    2023
  • 资助金额:
    $ 357.77万
  • 项目类别:
    Grant-in-Aid for JSPS Fellows
Joint U.S.-Japan Measures for Aging and Dementia Derived from the Prevention of Age-Related and Noise-induced Hearing Loss
美日针对预防与年龄相关和噪声引起的听力损失而导致的老龄化和痴呆症联合措施
  • 批准号:
    23KK0156
  • 财政年份:
    2023
  • 资助金额:
    $ 357.77万
  • 项目类别:
    Fund for the Promotion of Joint International Research (International Collaborative Research)
The Effects of Muscle Fatigability on Gait Instability in Aging and Age-Related Falls Risk
肌肉疲劳对衰老步态不稳定性和年龄相关跌倒风险的影响
  • 批准号:
    10677409
  • 财政年份:
    2023
  • 资助金额:
    $ 357.77万
  • 项目类别:
Characterizing gut physiology by age, frailty, and sex: assessing the role of the aging gut in "inflamm-aging"
按年龄、虚弱和性别表征肠道生理学特征:评估衰老肠道在“炎症衰老”中的作用
  • 批准号:
    497927
  • 财政年份:
    2023
  • 资助金额:
    $ 357.77万
  • 项目类别:
Role of AGE/RAGEsignaling as a driver of pathological aging in the brain
AGE/RAGE信号传导作为大脑病理性衰老驱动因素的作用
  • 批准号:
    10836835
  • 财政年份:
    2023
  • 资助金额:
    $ 357.77万
  • 项目类别:
Deciphering the role of osteopontin in the aging eye and age-related macular degeneration
破译骨桥蛋白在眼睛老化和年龄相关性黄斑变性中的作用
  • 批准号:
    10679287
  • 财政年份:
    2023
  • 资助金额:
    $ 357.77万
  • 项目类别:
Elucidation of the protein kinase NLK-mediated aging mechanisms and treatment of age-related diseases
阐明蛋白激酶NLK介导的衰老机制及年龄相关疾病的治疗
  • 批准号:
    23K06378
  • 财政年份:
    2023
  • 资助金额:
    $ 357.77万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Underlying mechanisms of age-related changes in ingestive behaviors: From the perspective of the aging brain and deterioration of the gustatory system.
与年龄相关的摄入行为变化的潜在机制:从大脑老化和味觉系统退化的角度来看。
  • 批准号:
    23K10845
  • 财政年份:
    2023
  • 资助金额:
    $ 357.77万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Targeting Age-Activated Proinflammatory Chemokine Signaling by CCL2/11 to Enhance Skeletal Muscle Regeneration in Aging
通过 CCL2/11 靶向年龄激活的促炎趋化因子信号传导以增强衰老过程中的骨骼肌再生
  • 批准号:
    478877
  • 财政年份:
    2023
  • 资助金额:
    $ 357.77万
  • 项目类别:
    Operating Grants
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了