How Early Life Inflammation Affects Brain Amyloid-Beta Accumulation Following Subsequent Inflammation In Aged Mice

Abstract

Alzheimer's disease (AD) is characterized by short term memory loss which progresses into dementia due to the buildup of amyloid beta (A-beta) plaques as well as neurofibrillary tangles. These pathologies in the brain disrupt neuronal signaling and lead to brain atrophy and cognitive deficits. While age is the greatest risk factor in developing this malady, inflammation has been implicated in initiating the production of A-beta in the brain. This study was designed to assess the effects of the bacterial endotoxin lipopolysaccharide (LPS) on inflammation and subsequent production of A-beta in the hippocampi of 22-25 month-old mice that had either received saline or LPS injections when at a young age (4-month-old). Aged C57BL/6J mice were given intraperitoneal injections of saline, and 4 hours later blood was drawn via cheek bleed in order to measure base levels of pro-inflammatory cytokines. The following day the same mice were given intraperitoneal injections of 125 micrograms/kg of LPS, and 4 hours later blood was drawn via cheek bleed in order to measure acute reaction levels of pro-inflammatory cytokines. These mice were injected with LPS for 2 more consecutive days before their hippocampi were removed and analyzed for levels of A-beta. A control group of aged mice only received saline injections during all 4 days of injections. We were unable to acquire significant cytokine data, but we showed that aged mice who received LPS when they were young had less hippocampal A-beta compared to aged mice that had only received saline when they were young.