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
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.