In the present study, we show that i.v. infusion of young monocytes does not have a significant effect on overall plaque load, however, does result in significant reductions of specific plaque sizes. These data suggest that young monocytes are able to gain entry into the brain or activate other pathways that result in plaque remodeling and possible clearance in the brain. However, it could be possible that monocyte entry into the brain is somewhat diminished due to the loss of certain surface markers immediately following bead isolation. However, we have shown that this expression reappears after 24 h, however, such findings could explain why we observe less positive effects on plaque deposition and cognition. In addition, it could be possible that monthly infusions of 5 x 106 monocytes might not be frequent enough to induce a significant reduction in amyloid plaque load. A previous study demonstrated that twice weekly infusions of CD11b+ bone marrow cells could arrest amyloid deposition in an AD transgenic mouse model. Thus, more frequent infusions may be required to attenuate amyloid deposition or a longer ICG-001 experimental set-up that provides more time for cells to rid the brain of amyloid. Others have shown that bone marrowderived cells are detected in mice as soon as 24 h and up to four weeks following hypoxic-ischemic brain injury despite injection 6 months prior. Further, we were interested in determining whether these alterations also translated into changes in cortical APP protein levels. Here, we report that no significant differences in APP expression were found in the cortex between APPSwDI mice given monocyte or saline infusions. This data suggests that monocyte infusions do not alter APP processing or expression in the cortex, however, it could also be possible that changes in APP protein levels are present at earlier stages of the disease. Microglia are considered the resident immune cells of the CNS, responsible for surveying the brain and responding to first signs of insult or injury. In both human AD and mouse transgenic AD models, activated microglia are found closely associated to amyloid plaques, indicating their potentially important role in A�� and plaque pathology. However, delineating the role of these cells in AD has proven difficult. In vitro and in vivo studies have shown that microglia can phagocytose A��, whereas, others have demonstrated that complete ablation of these cells has little to no effect on plaque deposition. Moreover, studies indicate that microglia might develop a proinflammatory or neurotoxic phenotype in response to A�� exposure, contributing to further disease aggravation and progression. Here, we show that Iba1 staining, a marker for microglial/SCH772984 abmole macrophage activation, is significantly reduced in animals receiving monocyte infusions. The observable morphological changes of these cells also points to diminished cell activation. These findings indicate that monocyte infusions could play a role in suppressing microglial activation. However, further investigations are needed to understand whether this also includes altering properties involved in phagocytosis, the release of neurotoxic species, and the release of proinflammatory cytokines. In addition to microglial activation, we were also interested in determining whether monocyte infusions could have a detrimental effect on cytotoxicity and neuroinflammation in the APPSwDI mouse brain. In this study, we demonstrated that monthly i.v. monocyte infusions do not significantly alter catalase, MMP-2 or proinflammatory cytokines in the cortices or plasma of APPSwDI mice.