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

Abstract

Two major active species of β-amyloid protein (Aβ), fibrillar Aβ1-42 (FAβ) and soluble Aβ1-42 oligomers (AβO), 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 FAβ and AβO on cognitive functions and hippocampal inflammatory response through a 30-days infusion of FAβ or AβO (144pmol/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 AβO-infused rats, compared to the FAβ-infused rats. AβO-induced neurodegeneration and ultrastructure damage in CA1 neurons were more remarkable than those induced by FAβ. Compared to FAβ, AβO exerted more potent effects on the expressions of inflammatory factors toll-like receptor 4 and TNF-α and activation of NF-κB signaling. Taken together, our results from in vivo model demonstrate that AβO is more neurotoxic than FAβ, and this neurotoxicity may be related to NF-κB-medicated inflammatory response.