Suppression of nuclear factor kappa B ameliorates astrogliosis but not amyloid burden in APPswe/PS1dE9 mice.

Neuroinflammation has been linked to the pathologies of Alzheimer's disease (AD), however, its effects on beta-amyloid (Abeta) burden are unclear. This study investigated the role of nuclear factor kappa B (NF-kappaB) in regulating neuroinflammation and Abeta deposition in a transgenic mouse model of AD. The APPswe/PS1dE9 mice and their wild-type controls received either the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC, i.p. 50 mg/kg daily) or saline starting at 7 months of age for 5 months. Expression of cyclooxygenase-2 (COX-2), tissue necrosis factor alpha (TNFalpha) precursor protein and microtubule-associated protein 2 was determined, and astrogliosis was assessed. Hippocampal and cortical levels of Abeta(1-40) and Abeta(1-42) were measured using ELISA. PDTC treatment effectively suppressed NF-kappaB signaling in APPswe/PS1dE9 mice as evidenced by the abolishment of COX-2 and TNFalpha induction. Inhibition of NF-kappaB further attenuated astrogliosis in the transgenic AD mice, yet markedly increased cerebral Abeta(1-42) burden. Our findings suggest that NF-kappaB can mediate induction of COX-2, TNFalpha and astrogliosis in APPswe/PS1dE9 mice. Additionally, these results support the idea that neuroinflammation contributes to the clearance of Abeta.