Soluble oligomers and fibrillar species of amyloid β-peptide differentially affect cognitive functions and hippocampal inflammatory response

Two major active species of beta-amyloid protein (A beta), fibrillar A beta 1-42 (FA beta) and soluble A beta 1-42 oligomers (A beta O), are known to play important roles in the pathogenesis of Alzheimer's disease. However, the differences between them are largely unknown. In this study, we explored the effects of FA beta and AM on cognitive functions and hippocampal inflammatory response through a 30-days infusion of FA beta or A beta O (144 pmol/d) into the left lateral ventricles of the rat brain. Morris water maze showed that the impairment of learning and memory functions was much more significant in the A beta O-infused rats, compared to the FA beta-infused rats. A beta O-induced neurodegeneration and ultrastructure damage in CA1 neurons were more remarkable than those induced by FA beta. Compared to FA beta, A beta O exerted more potent effects on the expressions of inflammatory factors toll-like receptor 4 and TNF-alpha and activation of NF-kappa B signaling. Taken together, our results from in vivo model demonstrate that A beta O is more neurotoxic than FA beta, and this neurotoxicity may be related to NF-kappa B-medicated inflammatory response. (C) 2012 Elsevier Inc. All rights reserved.