tTA constitutively induces tau expression via the TRE, but can be inactivated with doxycycline administration. Behavioral and histopathological characterization of rTg4510 mice demonstrated that overexpression of mutant human tau results in age-related increases in insoluble tau and NFTs, astrogliosis, UNC0224 synaptic and neuronal loss, and impairments in learning and memory, suggesting that this model captures at least some of the key components of human disease. Elevated levels of phosphorylated tau and neurofibrillary tangles lead to neurotoxicity, cognitive deficits, and behavioral symptoms in the class of Afobazole neurodegenerative disorders collectively called tauopathies. To better understand the 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 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.