糖尿病（DM）与Alzheimer病（AD）、血管性痴呆（VD）及轻度认知功能障碍（MCI）均关系密切，但DM性痴呆/MCI的发病机制尚不明了。近期研究提示AD/MCI患者血中的某些蛋白与AD/MCI有关，而AD与DM的蛋白质组学结果有一定的相似性。DM性痴呆/MCI患者无创体液中是否存在能用于其早期诊断的蛋白分子标志物？我们拟利用前期成功改进的非标定量蛋白质组学技术筛选DM性痴呆/MCI的血、尿差异蛋白质，用MetaCore、Reactome、Human Protein Atlas等软件确定其已知功能、组织分布等信息，用Spearmen Correlation关联分析及前期建立的尿蛋白质组疾病识别算法确定与DM性痴呆/MCI相关的血、尿蛋白，建立其血、尿蛋白质组数据库。本研究的预期结果不仅将增进我们对DM性痴呆/MCI发病机制的理解，并可望从分子水平寻找到其早期诊断的无创定量生物学标记。

Diabetes mellitus (DM) is associated with Alzheimer's disease (AD), vascular dementia (VD) and mild cognitive impairment (MCI), but the detailed pathological mechanism of dementia/MCI with DM is still not clear. Recent study suggested that some proteins found in AD/MCI patients' blood samples is associated with AD/MCI, and similarities in results of the proteomic studies between AD and DM were also found. Is it possible to find protein biomarkers in noninvasive body fluid specimens of dementia/MCI with DM patients for its early diagnosis? First, we will use the label-free proteomic technique, which has been successfully developed from lots of our early work, to find the differential proteins in blood and urine samples of the dementia/MCI with DM patients. Second, we will study functions and distribution information of these differential proteins using software like MetaCore, Reactome and Human Protein Atlas etc. Finally, we will certify those blood/urine proteins which are associated with dementia/MCI with DM using Spearmen Correlation association analysis and our newly established disease recognition algorithm of urine proteins, and set up the blood/urine proteomics database of dementia/MCI with DM. The perspective results of our study will not only increasing our understanding on the pathological mechanism of dementia/MCI with DM, but also will help us to find the noninvasive and quantitative biomarkers for its early diagnosis at the molecular level.

糖尿病（DM）与Alzheimer病（AD）、血管性痴呆（VD）及轻度认知功能障碍（MCI）均关系密切，但DM性痴呆/MCI的发病机制尚不明了。近期研究提示AD/MCI患者血中的某些蛋白与AD/MCI有关，而AD与DM的蛋白质组学结果有一定的相似性。DM性痴呆/MCI患者无创体液中是否存在能用于其早期诊断的蛋白分子标志物？我们按计划完成了研究对象收集并建立了相应临床资料数据库和血清、尿标本库；通过改进的非标定量蛋白质组学技术对DM性痴呆/MCI相关的血清、尿差异蛋白质进行了筛选；现正进行数据处理和结果分析，以确定与DM性痴呆/MCI相关的候选血/尿蛋白，并初步建立DM性痴呆/MCI病人的血清、尿蛋白质组数据库。当前研究结果显示T2DM+AD相对于T2DM组的尿差异蛋白，共有228个上调蛋白, 可能作为候选的生物标志物；用上调的228个尿差异蛋白作KEEG Pathway分析，其中有38个蛋白富集到多聚糖生物合成和代谢相关通路，有11个蛋白富集到了Alzheimer疾病相关通路T2DM+VD相对于T2DM组的尿差异蛋白，共有393个上调蛋白，可能作为候选的生物标志物。明年拟完成数据验证、结果整理、论文书写及投稿。本研究将确定与DM性痴呆/MCI相关的血、尿蛋白，建立其血、尿蛋白质组数据库。本研究的预期结果不仅将增进我们对DM性痴呆/MCI发病机制的理解，并可望从分子水平寻找到其早期诊断的无创定量生物学标记，为后续研究及其他国际国内同行研究提供重要参考。