Microglia, the resident innate immune cells of the central nervous system (CNS), have emerged as critical players in normal CNS function as well as in the progression of major disorders such as Alzheimer's disease (AD). Although microglia have been traditionally categorized into either the pro-inflammatory 'M1' or the anti-inflammatory 'M2' phenotype, new studies have uncovered a previously unappreciated spectrum of microglial phenotypes involved in a range of important processes including synaptic homeostasis and neurotrophic support. In order to address whether this spectrum is altered in AD, it is first necessary to elucidate the molecular signatures underlying these microglial phenotypes. Recent efforts have therefore applied next generation sequencing techniques and approaches such as weighted gene co-expression network analysis, a systems biology method for describing the correlation patterns among genes, to better understand these signatures at the genomic level. Remarkably, the most perturbed gene networks identified in AD brains fall squarely within microglial pathways and these findings are consistent with previous genome wide association studies linking specific microglial genes to AD risk. Furthermore, parallel work examining the peripheral immune system indicates that monocytes may exhibit some of the same gene network changes, opening the possibility of developing new peripheral biomarkers. This symposium will therefore focus on the identification of microglial gene network signatures associated with AD, how these phenotypes might be modulated to alter the course of AD pathology, and how a better understanding of peripheral immune biology may lead to the development of therapeutics and peripheral biomarkers for AD.
*Reception to follow.
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