Microglia antigen presentation in the CNS of Alzheimer's disease

PIS：Bradshaw，Elizabeth M.博士和Wassim Elyaman博士 标题：阿尔茨海默病患者中枢神经系统中的小胶质细胞抗原提呈 项目摘要/摘要 阿尔茨海默病(AD)是一种以进行性认知为特征的与年龄相关的神经退行性疾病 衰老和痴呆症。全基因组关联研究已经确定了新的AD易感基因。 有趣的是，其中几个基因座的相关基因与迟发性AD的免疫系统有关 (LOAD)，特别是先天免疫系统，包括人类白细胞抗原(HLA)区域。这个 人类白细胞抗原基因区域与负荷的发现进一步强调了这样一个问题： 小胶质细胞是中枢神经系统(CNS)的抗原提呈细胞，与渗透的T细胞相互作用， 在AD患者的海马体中观察到了哪些抗原，特别是哪些抗原 呈上了。同时，病原体假说也为可能的病原学获得了更多的支持。 公元一代的。我们建议利用我们对免疫系统的理解与尖端技术相结合 技术和获取AD患者的血液和脑尸检来确定这些神经侵袭性病原体 在阿尔茨海默病中具有神经毒性。对于这种应用，我们提出了一种多方面的方法来：1)识别多肽 由AD脑内高T细胞浸润区和低T细胞区小胶质细胞的MHC呈现 2)检测AD大鼠海马区T细胞的抗原反应性和表型， 以及3)确定小胶质细胞如何作为病原体的抗原提呈细胞来渗透T细胞。

PIs: Bradshaw, Elizabeth M., Ph.D. and Wassim Elyaman, Ph.D. Title: Microglia antigen presentation in the CNS of Alzheimer's disease Project Summary/Abstract 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 (LOAD), specifically the innate immune system, including the human leukocyte antigen (HLA) region. The finding of the HLA region being genetically associated with LOAD further emphasizes the question of how microglia, the antigen-presenting cells of the central nervous system (CNS), interact with infiltrating T cells, which have been observed in the hippocampus of AD patients, and specifically what antigens are being presented. 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 combined with cutting-edge technology and access to AD patient blood and brain autopsies to determine if these neuroinvasive pathogens are neurovirulent in AD. For this application, we propose a multifaceted approach to: 1) identify the peptides being presented by the MHC of microglia in the AD brain in regions of high T cell infiltration and areas of low T cell infiltration; 2) examine the antigen reactivity and phenotype of T cells infiltrating the hippocampus in AD, and 3) determine how microglia function as antigen-presenting cells of pathogens to infiltrating T cells.