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 (Aβ) burden are unclear. This study investigated the role of nuclear factor kappa B (NF-κB) in regulating neuroinflammation and Aβ deposition in a transgenic mouse model of AD. The APPswe/PS1dE9 mice and their wild-type controls received either the NF-κB 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 (TNFα) precursor protein and microtubule-associated protein 2 was determined, and astrogliosis was assessed. Hippocampal and cortical levels of Aβ1-40 and Aβ1-42 were measured using ELISA. PDTC treatment effectively suppressed NF-κB signaling in APPswe/PS1dE9 mice as evidenced by the abolishment of COX-2 and TNFα induction. Inhibition of NF-κB further attenuated astrogliosis in the transgenic AD mice, yet markedly increased cerebral Aβ1-42 burden. Our findings suggest that NF-κB can mediate induction of COX-2, TNFα and astrogliosis in APPswe/PS1dE9 mice. Additionally, these results support the idea that neuroinflammation contributes to the clearance of Aβ.