Identification of key neutrophil extracellular trap genes in Alzheimer's disease

Abstract

Background Alzheimer's disease (AD) is a neurodegenerative disorder that is associated with neuroinflammation. Neutrophil extracellular traps (NETs) are web-like structures that cause inflammation, but its involvement in AD pathogenesis is unclear. Objective This study aimed to identify key NETs related genes associated with AD. Methods A total of 180 samples from the GSE122063 and GSE36980 dataset were obtained from the GEO repository. The representative genes were obtained, and its diagnostic performance was evaluated by analyzing operating characteristic curves. Consensus clustering and principal component analysis were performed to cluster AD samples. Gene ontology, KEGG pathway enrichment, and protein interaction network were analyzed. Peripheral blood samples were collected from 5 AD patients and 5 healthy donors to determine the expression of representative proteins or genes using WB, ELISA, and RT-qPCR. Results A total of 297 differentially expressed genes (DEGs) were associated with AD, 18 NETs genes showed potential diagnostic value. NETs genes expression effectively distinguished AD patients into 2 subgroups. The AD1 cluster showed higher abundance of activated dendritic cells, monocytes, and neutrophils, the AD2 cluster showed higher levels of naive B cells, eosinophils, and activated NK cells. We randomly selected and measured the levels representative genes in AD patients. The levels of NETs and CCL2, TLR2 expressions were significantly increased, whereas the level of BDNF was significantly decreased in AD patients comparing with healthy controls. Conclusions This study identified key NET genes including BDNF, CCL2, and TLR2 to be associated with AD pathogenesis and classification.