Helicobacter pylori filtrate impairs spatial learning and memory in rats and increases β-amyloid by enhancing expression of presenilin-2

Helicobacter pylori (H. pylon) infection is related with a high risk of Alzheimer's disease (AD), but the intrinsic link between H. pylon infection and AD development is still missing. In the present study, we explored the effect of H. pylori infection on cognitive function and beta-amyloid production in rats. We found that intraperitoneal injection of H. pylon filtrate induced spatial learning and memory deficit in rats with a simultaneous retarded dendritic spine maturation in hippocampus. Injection of H. pylon filtrate significantly increased A beta(42) both in the hippocampus and cortex, together with an increased level of presenilin-2 (PS-2), one key component of gamma-secretase involved in A beta production. Incubation of H. pylon filtrate with N2a cells which over-express amyloid precursor protein (APP) also resulted in increased PS-2 expression and A beta(42) overproduction. Injection of Escherichia coli (E.coli) filtrate, another common intestinal bacterium, had no effect on cognitive function in rats and A beta production in rats and cells. These data suggest a specific effect of H. pylon on cognition and A beta production. We conclude that soluble surface fractions of H. pylon may promote A beta(42) formation by enhancing the activity of gamma-secretase, thus induce cognitive impairment through interrupting the synaptic function.