阿尔茨海默病（Alzheimer’s disease，AD）已成为全球公共卫生问题，但目前对其病因病机远未阐明。最新研究表明，神经炎症与AD发病机制关系密切。本研究团队将基于前期积累，利用高通量外显子测序技术结合影像遗传学策略，在中国汉族老年人群中同期选择主观记忆损害、AD所致轻度认知功能损害、轻度AD以及匹配的健康对照组，分层探讨AD谱系人群神经炎症指标在AD发生、发展中的作用：分析外周血和脑脊液中与神经炎症相关指标的差异性，寻找AD谱系人群不同阶段的生物标志物；筛选神经炎症系统与AD关联的关键易感基因，分析重要候选基因的集聚效应对AD谱系人群病理表型、临床表征以及对AD病理相关脑区的体积、脑结构和功能网络的模式特征和信息整合功能的影响，揭示神经炎症系统易感基因对AD谱系人群脑结构及功能网络的调控机制，建立基于神经炎症系统的、不同病理阶段的AD早期诊断识别系统，并为将来随访研究提供依据。

Alzheimer's disease (AD) has become a global public health issue, however, its etiology and pathogenesis is far from clear. Recent studies have suggested that the neural inflammation was closely associated with the pathogenesis of AD. Therefore, build on our previous findings, we will investigate the potential influence of candidate biomarkers from neural inflammation on the occurrence and progress of AD spectrum population including subjective memory impairment, mild cognitive impairment due to AD, mild AD, and well-matched cognitive normal healthy elders, by using whole gene exon sequencing technology combined with imaging genetics strategy. Firstly, we will detect the difference of neural inflammation related indicators in peripheral blood and cerebrospinal fluid, and determine the potential candidate biomarkers at the different AD stages; Secondly, we will screen the key susceptible genes associated with AD in neural inflammation system, and explore the clustering effects of these candidate genes on clinical and pathological phenotypes of AD. Further, we will investigate the effects of these genes on the gray matter volumes of vulnerable brain regions, the patterns and information integration of structural and functional networks related to AD. The current study might reveal the genetic regulatory mechanism on brain structure and function networks targeting on neural inflammation system for AD spectrum population. Taken together, we will integrate above findings to establish an early diagnosis system for AD high-risk population based on neural inflammation at the different pathological stages of AD, and provide empirical evidence for future follow-up study.