A potential role for LPS-induced inflammation in the induction of Alzheimer's disease-related pathology and cognitive deficits

Abstract

Alzheimer's disease (AD) is characterized by neuronal cell death in regions of the adult brain, including the hippocampus, due to formation of amyloid-beta plaques and neurofibrillary tangles. Inflammation has been implicated in the onset and progression of these pathologies. Our study was designed to create an animal model of peripheral inflammation-induced AD-like pathologies using the bacterial endotoxin Lipopolysaccharide (LPS). C57BL/6J mice were given intraperitoneal injections of LPS or saline for 7 days. Hippocampal tissue from animals receiving LPS contained significantly higher levels of amyloid-beta 1-42 than did control animals. We also demonstrated that one injection of LPS leads to sickness behavior, but 7 days does not, implicating endotoxin tolerance. To determine if elevation in amyloid-beta 1-42 might inhibit learning, cognitive testing in both MWM and CFC, revealed learning deficits in LPS treated mice. In summary multiple injections of LPS resulted in increased amyloid-beta 1-42, in the hippocampus and cognitive deficits in mice.