Do repeated bouts of inflammation lead to sustained elevation of amyloid beta in the brain?

Abstract

One of the main biological hallmarks of Alzheimer's disease is the presence of amyloid beta plaques. Amyloid beta (A?) is a peptide fragment cleaved from the amyloid precursor protein on the membranes of neurons which accumulates in the synapses and blocks signaling of neurotransmitters, resulting in damage and death to neurons and ultimately atrophy in the brain. A? concentration is particularly apparent in the hippocampus therefore having negative impact on learning and memory, characteristics of Alzheimer's disease. Scientists have found a strong link between chronic inflammation and the dysregulation of A? resulting in the increasing influx of A? in the brain without compensatory clearance. Our study sought to determine how long A? remained elevated in the hippocampus of mice following 7 days of lipopolysaccharide LPS-induced inflammation. We injected C57BL/6J mice with 7 days of LPS or saline and assessed cognitive function and levels of A? at 2, 16, and 23 days following injections and found that by 23 days A? was returned to levels similar to controls. We then sought to determine if a repeated bout of LPS-induced inflammation at some point following the first bout when A? was still significantly elevated would result in an even greater elevation of A? as well as greater cognitive dysfunction than that following the first bout. Unexpectedly, we found that A? levels in the LPS- injected mice were similar to saline controls following the second bout of inflammation. Either endotoxin tolerance or the activity of B-1 cells in the peritoneal cavity may explain the unexpected result