|Abstract||Alzheimer's disease (AD) is a progressive disorder characterized by neuronal cell death and atrophy in regions of the adult brain, including the hippocampus and cortex. Two hallmark pathologies of AD are extracellular amyloid-beta (A-beta) plaques and intracellular neurofibrillary tangles. Presence of these pathologies can limit normal cell signaling properties leading to learning and memory deficits and, ultimately, cell death. Chronic inflammation has been implicated in the onset and progression of these AD pathologies. Our lab has previously shown that peripheral injections of a bacterial mimetic leads to increased A-beta levels in the mouse hippocampus, as well deficits in hippocampus-dependent learning. The current study was designed to further our understanding of peripheral inflammation-induced AD-like pathology by using polyinosinic:polycytidylic acid (Poly I:C) which produces an inflammation similar to that caused by double-stranded viral RNA. Mice were given intraperitoneal (i.p.) injections of Poly I:C or saline for 7 consecutive days. Similar to our findings using the bacterial mimetic LPS, hippocampal tissue from animals receiving peripheral Poly I:C contained significantly higher levels of A-beta peptide over that found in saline injected control animals. However, unlike LPS, 7 consecutive injections of Poly I:C leads to sickness behavior that does not disappear until 48 hours after the final injection. Cognitive testing at that time revealed no deficit in hippocampus-dependent learning. Our studies implicate that both bacterial and viral inflammation can produce elevated levels of A-beta in the hippocampus, but pilot data suggests a minimum level of A-beta may be necessary to produce cognitive deficits.