Chronic administration of R-flurbiprofen attenuates learning impairments in transgenic amyloid precursor protein mice.

Background: Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of Alzheimer's disease (AD). We and others have shown that certain NSAIDs reduce secretion of Abeta42 in cell culture and animal models, and that the effect of NSAIDs on Abeta42 is independent of the inhibition of cyclooxygenase by these compounds. Since Abeta42 is hypothesized to be the initiating pathologic molecule in AD, the ability of these compounds to lower Abeta42 selectively may be associated with their protective effect.

Novel rat Alzheimer's disease models based on AAV-mediated gene transfer to selectively increase hippocampal Abeta levels.

Background: Alzheimer's disease (AD) is characterized by a decline in cognitive function and accumulation of amyloid-beta peptide (Abeta) in extracellular plaques. Mutations in amyloid precursor protein (APP) and presenilins alter APP metabolism resulting in accumulation of Abeta42, a peptide essential for the formation of amyloid deposits and proposed to initiate the cascade leading to AD. However, the role of Abeta40, the more prevalent Abeta peptide secreted by cells and a major component of cerebral Abeta deposits, is less clear.

Intracranial adeno-associated virus-mediated delivery of anti-pan amyloid beta, amyloid beta40, and amyloid beta42 single-chain variable fragments attenuates plaque pathology in amyloid precursor protein mice.

Accumulation of amyloid beta protein (Abeta) aggregates is hypothesized to trigger a pathological cascade that causes Alzheimer's disease (AD). Active or passive immunizations targeting Abeta are therefore of great interest as potential therapeutic strategies. We have evaluated the use of recombinant anti-Abeta single-chain variable fragments (scFvs) as a potentially safer form of anti-Abeta immunotherapy.

Interleukin-1 receptor 1 knockout has no effect on amyloid deposition in Tg2576 mice and does not alter efficacy following Abeta immunotherapy.

Background: Microglial activation has been proposed to facilitate clearance of amyloid beta protein (Abeta) from the brain following Abeta immunotherapy in amyloid precursor protein (APP) transgenic mice. Interleukin-1 receptor 1 knockout (IL-1 R1-/-) mice are reported to exhibit blunted inflammatory responses to injury. To further define the role of IL-1-mediated inflammatory responses and microglial activation in this paradigm, we examined the efficacy of passive Abeta immunotherapy in Tg2576 mice crossed into the IL-1 R1-/- background.

Exacerbation of intestinal permeability in rats after a two-hit injury: burn and Enterococcus faecalis infection.

Objective: To determine alterations in intestinal epithelial permeability to solutes in burn injured rats with and without Enterococcus faecalis infection and the role of neutrophils in the intestinal permeability changes.

Design: Prospective sham-controlled animal study.

Setting: University research laboratory.