Intersection of HSV-1 and microglial genetics in AD

AD 中 HSV-1 和小胶质细胞遗传学的交叉点

基本信息

项目摘要

Project Summary Alzheimer’s disease (AD) is an age-related neurodegenerative disease characterized by progressive cognitive decline and dementia. Genome-wide association studies have identified novel AD susceptibility loci. Interestingly the associated genes at several of these loci implicate the immune system in late-onset AD, specifically the innate immune system. Many recent lines of evidence suggest that the immune system plays a key role in AD initiation and progression, but the actual mechanistic dysfunction of the immune system in this neurodegenerative disease remains unknown. Genetic studies and pathology hint that the immune system’s ability to mount a productive response has been lost in AD with detrimental consequences. Post-mortem pathology of individuals with AD reveals an infiltration of T cells in the hippocampus, a region expected to be immune privileged, leading to speculation that AD might have an infectious component to its etiology or progression. In parallel, the pathogen hypothesis has garnered more support for a possible pathogenic etiology of AD. We propose to leverage our understanding of the immune system to determine if the immune response to the neuroinvasive pathogen human simplex virus (HSV)-1 is modulated by AD genetic associations, leading to increased risk for AD. We will take a comprehensive approach using cutting-edge tools to explore this hypothesis in AD. Combining genetics, human immunology, transcriptomics, virology, in vitro models, computational biology and epidemiology, we will dissect the interaction between HSV-1 infections and AD genetics. For this application, we propose a multifaceted approach using cutting-edge technology to: 1) identify the microglia response to HSV-1 infection based on each individual’s genetic background; 2) examine how these microglia function as antigen-presenting cells to T cells, a key cell type in resolving active infections; and 3) determine the interaction of HSV-1 and AD genetics in two well-establish cohorts and one anti-viral clinical trial in AD.
项目总结

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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Elizabeth M Bradshaw其他文献

BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 implicated in Tau pathology
BIN1 蛋白亚型在星形胶质细胞、神经元和小胶质细胞中差异表达:神经元和星形胶质细胞 BIN1 与 Tau 病理有关
  • DOI:
    10.1101/535682
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    M. Taga;V. Petyuk;Charles C. White;Galina Marsh;Yiyi Ma;Hans Klein;Sarah M. Connor;Anthony Khairallah;M. Olah;J. Schneider;Richard M Ransohoff;David A. Bennett;Andrea Crotti;Elizabeth M Bradshaw;P. D. De Jager
  • 通讯作者:
    P. D. De Jager

Elizabeth M Bradshaw的其他文献

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{{ truncateString('Elizabeth M Bradshaw', 18)}}的其他基金

Intersection of HSV-1 and microglial genetics in AD
AD 中 HSV-1 和小胶质细胞遗传学的交叉点
  • 批准号:
    10381305
  • 财政年份:
    2021
  • 资助金额:
    $ 80.35万
  • 项目类别:
Microglia antigen presentation in the CNS of Alzheimer's disease
阿尔茨海默病中枢神经系统中小胶质细胞抗原呈递
  • 批准号:
    10360538
  • 财政年份:
    2020
  • 资助金额:
    $ 80.35万
  • 项目类别:
Microglia antigen presentation in the CNS of Alzheimer's disease
阿尔茨海默病中枢神经系统中小胶质细胞抗原呈递
  • 批准号:
    10162474
  • 财政年份:
    2020
  • 资助金额:
    $ 80.35万
  • 项目类别:
Microglia antigen presentation in the CNS of Alzheimer's disease
阿尔茨海默病中枢神经系统中小胶质细胞抗原呈递
  • 批准号:
    9976128
  • 财政年份:
    2020
  • 资助金额:
    $ 80.35万
  • 项目类别:
Microglia antigen presentation in the CNS of Alzheimer's disease
阿尔茨海默病中枢神经系统中小胶质细胞抗原呈递
  • 批准号:
    10558658
  • 财政年份:
    2020
  • 资助金额:
    $ 80.35万
  • 项目类别:
Microglia antigen presentation in the CNS of Alzheimer's disease
阿尔茨海默病中枢神经系统中小胶质细胞抗原呈递
  • 批准号:
    10827697
  • 财政年份:
    2020
  • 资助金额:
    $ 80.35万
  • 项目类别:
Influence of genotype on microglia phenotype and function in PD
帕金森病中基因型对小胶质细胞表型和功能的影响
  • 批准号:
    9120948
  • 财政年份:
    2015
  • 资助金额:
    $ 80.35万
  • 项目类别:
Influence of genotype on microglia phenotype and function in PD
帕金森病中基因型对小胶质细胞表型和功能的影响
  • 批准号:
    8965189
  • 财政年份:
    2015
  • 资助金额:
    $ 80.35万
  • 项目类别:
Influence of genotype on monocyte and microglia phenotype and function in Parkinson's disease (PD)
基因型对帕金森病(PD)单核细胞和小胶质细胞表型和功能的影响
  • 批准号:
    8928814
  • 财政年份:
    2014
  • 资助金额:
    $ 80.35万
  • 项目类别:
Altered monocyte function in relation to the CD33 Alzheimers disease locus
与 CD33 阿尔茨海默病基因座相关的单核细胞功能改变
  • 批准号:
    8549085
  • 财政年份:
    2012
  • 资助金额:
    $ 80.35万
  • 项目类别:

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