Down syndrome (DS) is characterized by mental retardation and the development of Alzheimer's disease (AD). The reason for this development is not yet clear. Ts65Dn mice were used in this study. We collected their hippocampi and identified protein biomarkers using isobaric tags for relative and absolute quantitation (iTRAQ). We described the biochemical characteristics of proteins and explored their complicated network using GOA, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and network

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... analysis. There were 374 significant differential proteins in the hippocampi of Ts65Dn mice. These were mainly binding proteins, related to single-organism and cellular processes. KEGG pathway analysis revealed that the insulin-signaling pathway was enriched with DS. Using PAJEK, a network of protein interactions was constructed and the top ten hub proteins were FYN, YBX1, VIM, PRKACA, EWSR1, H2AFX, CACNA1A, PTN, TFCP2L1 and CRKL. Through preliminarily discovered differentially expressed proteins by iTRAQ and bioinformatics analysis, we concluded that these proteins could be closely related to the neurological deficits of DS.