To better understand the Aminophylline molecular events leading to pathology and neurotoxicity, we took an unbiased approach to characterize gene expression over time in the rTg4510 mouse, and to correlate these changes with functional consequences on behavioral phenotypes. Strikingly, the largest and most significant gene expression changes overlapped extensively with the immune function networks that were recently identified in AD by connecting genes with related expression signatures and overlaying correlations with clinical severity. These networks are likely to encompass a number of cell types, including microglia, astrocytes, infiltrating monocytes, neurons, and perhaps lymphocytes and other inflammatory cells. Increased expression of these genes could represent an increase in the number of cells in which they are expressed, an upregulation of expression in Taurine existing cells, or a combination of both. Gene expression networks in rTg4510 mice generated by IPA appeared very similar to those identified in AD, with complement pathways representing a major subnetwork centered around a hub formed by the gene, Tyrobp. While complement activation is a well-described pathological feature of AD, the role of complement in neurodegenerative disease has received renewed interest as genome-wide association studies have identified alleles of the gene encoding complement component receptor 1, CR1, as conferring substantial risk for AD. Furthermore, Tyrobp, which encodes for the protein DAP12, has consistently been identified as the hub of the complement subnetwork of the microglial network. In addition, Tyrobp is the coreceptor for Trem2, which has also been genetically associated with AD risk. Both genes are amongst the top upregulated genes in rTg4510 in this study and are closest neighbors by hierarchical clustering, suggesting coregulation. Age-dependent increases in neuroinflammatory genes also coincided with age-dependent decreases in markers of synaptic activity, such as Arc and Homer2,, and upregulation of markers of inhibitory interneuron activity in the hippocampus.