Journal of Alzheimers Disease & Parkinsonism
Open Access

Abstract

Cells of the innate immune system including monocytes and macrophages are the first line of defence against infections and are critical regulators of the inflammatory response. These cells express toll-like receptors (TLRs), innate immune receptors which govern tailored inflammatory gene expression patterns. Monocytes, which produce pro-inflammatory mediators, are readily recruited to the central nervous system (CNS) in neurodegenerative diseases. This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP). The expression of CD11b, TLR4 and TLR2 was increased in MDMs from the LP group when compared to HP cohort. MDMs from both groups responded robustly to treatment with the TLR4 activator, lipopolysaccharide (LPS), in terms of cytokine production. Significantly, MDMs from the LP group displayed hypersensitivity to LPS exposure. Overall these findings define differential receptor expression and cytokine profiles that occur in MDMs derived from a cohort of IQ memory-discrepant individuals. These changes are indicative of inflammation and may be involved in the prodromal processes leading to the development of neurodegenerative disease.

Biography

Eric Downer graduated from Trinity College Dublin (TCD) with a first class honors degree in Physiology (2001), and a Ph.D. in Neuroscience (2005). He began his postdoctoral research career in the Physiology department at TCD with Prof. Marina Lynch (2005-2008) where his research focused on the signaling events underlying the neuroinflammatory conditions that are associated with brain ageing, particularly the mechanisms controlling microglial cell activation. Subsequently he was awarded a postdoctoral fellowship from the Irish Research Council for Science Engineering and Technology that enabled him to develop a research programme focused on the neuroimmunomodulatory effects of cannabinoids. This research programme was based with Prof. Paul Moynagh at the Institute of Immunology, NUI Maynooth (2008-2010). In 2011 he returned as a senior research fellow with Prof. Marina Lynch at the Trinity College Institute of Neuroscience, TCD, also acting as co-coordinator of the structured PRTLI PhD programme at TCD during this time (2012).