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 (A beta) burden are unclear. This study investigated the role of nuclear factor kappa B (NF-kappa B) in regulating neuroinflarnmation and A beta deposition in a transgenic mouse model of AD. The APPswe/PS1dE9 mice and their wild-type controls received either the NF-kappa B 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 (TNF alpha) precursor protein and microtubule-associated protein 2 was determined, and astrogliosis was assessed. Hippocampal and cortical levels of A beta(1-40) and A beta(1-42) were measured using ELISA. PDTC treatment effectively suppressed NF-kappa B signaling in APPswe/PS1dE9 mice as evidenced by the abolishment of COX-2 and TNFa induction. Inhibition of NF-kappa B further attenuated astrogliosis in the transgenic AD mice, yet markedly increased cerebral A beta(1-42) burden. Our findings suggest that NF-kappa B can mediate induction of COX-2, TNF alpha and astrogliosis in APPswe/PS1dE9 mice. Additionally, these results support the idea that neuroinflarnmation contributes to the clearance of A beta. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.