在外周血中发现老化及阿尔兹海默病（AD）的DNA甲基化标志有重要的意义。但是，由于各类外周血细胞的DNA甲基化模式不同，在外周全血中识别的老化及老化相关疾病的分子标志的细胞来源与功能意义尚不明确。在预实验中，我们初步识别了外周血CD4+T细胞与老化相关的甲基化标志及外周血白细胞中与AD相关的甲基化标志，并据此发现了5个关键的与CD4+T细胞老化相关的AD发病风险候选标志（位于基因CUL5、RNPEPL1、CTDP1、PKMYT1和ITGAX启动子区域）。本课题拟进一步分析CD4+T细胞的老化DNA甲基化标志及相应的功能通路特征；识别CD4+T细胞中与AD相关的DNA甲基化标志及相应的功能通路特征，并分析AD标志在外周全血中的可呈现性；验证与CD4+T细胞老化相关的AD关键风险标志及其在AD外周全血中的可呈现性。本课题对探究老化及AD相关的免疫损伤机制及识别AD的风险标志兼具理论与应用价值。

It's important to identify DNA methylation markers in whole blood for aging or age-related diseases such as Alzheimer's disease (AD). However, as different leukocyte subtypes have different DNA methylation patterns, the origin and functional significance of whole-blood based methylation markers for aging and age-related diseases are unclear. In a pre-experiment we have identified CpG methylation markers for aging from CD4 T cells which could also be presented in whole blood, and CpG methylation markers from whole blood for AD which could not be influenced by the cell proportions changes. Here, we will further identify five DNA methylation markers for aging and their corresponding functional injury signatures located in the promoter region of CUL5、RNPEPL1、CTDP1、PKMYT1 and ITGAX, and DNA methylation markers for AD and their functional injury signatures from CD4 T cells, and analyze the presentation of such markers in whole blood. Then, we will verify the risk factors associated with aging in AD CD4 T cellss and verify their presentation in AD whole blood. Results of this research would have extensive importance in the investigation of mechanism of aging related immune injury and mechanism of AD and the identification of risk factor for AD.