The time courses of levels of multiple plasma and cerebrospinal fluid (CSF) cytokines in patients with Alzheimer disease (AD) and in age-matched control subjects were compared. Interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, granulocyte-macrophage colony-stimulating factor, interferon-γ, and tumor necrosis factor alpha levels were measured 7 times over a 24-hour period in plasma and CSF using a lumbar catheter. Baseline plasma and CSF cytokine levels were found to be similar in AD and control subjects. However, the CSF levels of all measured cytokines, except IL-6 and IL-8, diverged over time between AD and control subjects, such that CSF cytokine levels in AD subjects were higher than in controls. This difference was greatest at 24 hours after the insertion of the lumbar catheter. In contrast, no differences in cytokine trajectories were seen in plasma. These data suggest that the neuroinflammatory response to lumbar catheter placement differs between AD and control subjects.