Network Pharmacology-Based and Experimental Identification of the Effects of Quercetin on Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the neurodegenerative brain disorders inducing nearly half of dementia cases, and the diagnosis and treatment of AD are the primary issues clinically. However, there is a lack of effective biomarkers and drugs for AD diagnosis and therapeutics so far. In this study, bioinformatics analysis combined with an experimental verification strategy was used to identify the biomarkers and the quercetin targets for AD diagnosis and treatment. First, differentially expressed genes in the AD brain were identified by microarray data analysis. Second, quercetin, a predominant flavonoid, was used to screen the target genes. Third, the drug–disease network was determined, and the target genes of quercetin treatment were obtained in AD-related HT-22 cell-based assay. Six genes, including MAPT, PIK3R1, CASP8, DAPK1, MAPK1, and CYCS, were validated by the system pharmacology analysis in the hippocampus samples of AD patients. The results suggested that MAPT, PIK3R1, CASP8, and DAPK1 were significantly increased, but MAPK1 and CYCS were significantly decreased in HT-22 cells after Aβ1-42 treatment. Moreover, MAPK1 and CYCS were markedly increased, but MAPT, PIK3R1, CASP8, and DAPK1 were markedly decreased after quercetin treatment in these HT-22 cells. Altogether, MAPT, PIK3R1, CASP8, DAPK1, MAPK1, and CYCS are all the biomarkers for AD diagnosis and the targets of quercetin treatment, and our findings may provide valuable biomarkers for AD diagnosis and treatment.