Background: Alzheimer’s Disease (AD) and Type 2 Diabetes Mellitus (T2DM) have an increased incidence in modern society. Although increasing evidence has supported the close linkage between these two disorders, the inter-relational mechanisms remain to be fully elucidated.

Objective: The primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and T2DM.

Methods: We downloaded the microarray data of AD and T2DM from the Gene Expression Omnibus (GEO) database and constructed co-expression networks by Weighted Gene Co-Expression Network Analysis (WGCNA) to identify gene network modules related to AD and T2DM. Then, Gene Ontology (GO) and pathway enrichment analysis were performed on the common genes existing in the AD and T2DM related modules by clusterProfiler and DOSE package. Finally, we utilized the STRING database to construct the protein-protein interaction network and found out the hub genes in the network.

Results: Our findings indicated that seven and four modules were the most significant with AD and T2DM, respectively. Functional enrichment analysis showed that AD and T2DM common genes were mainly enriched in signaling pathways such as circadian entrainment, phagosome, glutathione metabolism and synaptic vesicle cycle. Protein-protein interaction network construction identified 10 hub genes (CALM1, LRRK2, RBX1, SLC6A1, TXN, SNRPF, GJA1, VWF, LPL, AGT) in AD and T2DM shared genes.

Conclusion: Our work identified common pathogenesis of AD and T2DM. These shared pathways might provide a novel idea for further mechanistic studies and hub genes that may serve as novel therapeutic targets for diagnosis and treatment of AD and T2DM.

背景：阿尔茨海默病 (AD) 和 2 型糖尿病 (T2DM) 在现代社会的发病率有所增加。尽管越来越多的证据支持这两种疾病之间的密切联系，但相互关系的机制仍有待充分阐明。

目的：本研究的主要目的是探讨 AD 和 T2DM 的共同病理生理机制。

方法：我们从基因表达综合（GEO）数据库中下载AD和T2DM的微阵列数据，并通过加权基因共表达网络分析（WGCNA）构建共表达网络，以识别与AD和T2DM相关的基因网络模块。然后，通过clusterProfiler和DOSE包对AD和T2DM相关模块中存在的共同基因进行基因本体（GO）和通路富集分析。最后，我们利用STRING数据库构建蛋白质-蛋白质相互作用网络，找出网络中的枢纽基因。

结果：我们的研究结果表明，七个和四个模块分别对 AD 和 T2DM 最重要。功能富集分析表明，AD和T2DM共同基因主要富集在昼夜节律夹带、吞噬体、谷胱甘肽代谢和突触小泡循环等信号通路中。蛋白质-蛋白质相互作用网络构建确定了 AD 和 T2DM 共享基因中的 10 个中枢基因（CALM1、LRRK2、RBX1、SLC6A1、TXN、SNRPF、GJA1、VWF、LPL、AGT）。

结论：我们的工作确定了 AD 和 T2DM 的常见发病机制。这些共享途径可能为进一步的机制研究和中枢基因提供新的思路，这些基因可以作为诊断和治疗 AD 和 T2DM 的新治疗靶点。