Down-Regulation of Insulin Like Growth Factor 1 Involved in Alzheimer's Disease via MAPK, Ras, and FoxO Signaling Pathways.

Abstract

The inability to halt or even delay the course of Alzheimer's disease (AD) forces the development of new molecular signatures and therapeutic strategies. Insulin like growth factor 1 (IGF1) is a promising target for AD treatment, yet exact mechanisms of AD ascribed to IGF1 remain elusive. Herein, gene expression profiles of 195 samples were analyzed and 19,245 background genes were generated, among which 4,424 differentially expressed genes (DEGs) were overlapped between AD/control and IGF1-low/high groups. Based on such DEGs, seven co-expression modules were established by weight gene correlation network analysis (WGCNA). The turquoise module had the strongest correlation with AD and IGF1-low expression, the DEGs of which were enriched in GABAergic synapse, long-term potentiation, mitogen-activated protein kinase (MAPK), Ras, and forkhead box O (FoxO) signaling pathways. Furthermore, cross-talking pathways of IGF1, including MAPK, Ras, and FoxO signaling pathways were identified in the protein-protein interaction network. According to the area under the curve (AUC) analysis, down-regulation of IGF1 exhibited good diagnostic performance in AD prediction. Collectively, our findings highlight the involvement of low IGF1 in AD pathogenesis via MAPK, Ras, and FoxO signaling pathways, which might advance strategies for the prevention and therapy of AD based on IGF1 target.