Queensland Brain Institute, University of Queensland
The initiation of an inflammatory response is critical to the survival of an organism. However, when inflammation fails to reach resolution, a chronic inflammatory state may occur, and it becomes a major cofactor in Alzheimer’s disease (AD). Comprehending the biological basis for altered innate immunity and inflammation in AD is a challenge that has substantial clinical importance, as restoration or preservation of immunological responses is likely to have a great importance to the lengthening of healthier lifespan. The discoveries that resolution of inflammation is a highly coordinated and active process controlled by endogenous pro-resolving and anti-inflammatory mediators, and that inflammatory cells undergo classical and alternative activation, highlight new potential molecular targets to regulate inflammation and treat chronic inflammatory diseases. Here, we will discuss novel findings from studies in human samples that demonstrate a severe impairment in signalling pathways associated with the regulation of inflammatory resolution. In addition, pre-clinical data will be presented to support the idea that restoring the activity of regulatory anti-inflammatory interleukins or pro-resolving lipid pathways can elicit protective immunity and mitigate AD-like pathology. In the future, it may be possible to generate therapies to regenerate and/or replace the endogenous inflammatory resolution pathways to prevent and/or treat AD.