Résumé
Initially described as passive elements that “fill the spaces around the neurons” (Virchow et al. 1856), glial cells are now recognized to play key homeostatic and supportive roles in the CNS. Under physio-pathological conditions, they become reactive and are critically involved in the brain response to the homeostasis changes. Interestingly, the development of approaches based on the Next-Generation Sequencing (NGS) technology demonstrated that glial reaction is not an all-or-none process. Rather, it highlighted the diversity of reactive glial cells and raised the possibility that different glial cell subtypes could have either beneficial, neutral or deleterious effects on neuronal functions.Recent genetic studies have underlined the key roles of microglia in Alzheimer Disease (AD), however their contribution to the disease progression is still poorly understood. In particular, whether microglia play beneficial and/or detrimental roles to the disease progression remains heavily debated. One hypothesis is that this duality of effects is carried by different subtypes of reactive microglia. Interestingly, in AD, microglia clustered around plaques have marked different phenotypes than those away from plaques, underlining microglia diversity in this disease.In this presentation, we will show how laser microdissection and RNAseq approaches can be combined to improve our understanding of the role of microglia cells during AD progression. Moreover, we will highlight the use of single-cell RNA-seq approaches to decipher the heterogeneity of microglia in the early phase of the disease. To conclude, we will discuss the advantages, pitfalls, and limitations of these NGS-based approaches and will underline how further development may improve our understanding of microglia’ roles in AD. Glial cell heterogeneity represents both a challenge and an opportunity: the existence of distinctive subpopulations of glial cells support the design of specific treatments targeting the particular subpopulations. NGS based approaches are highly relevant to those questions since they allow unbiased subpopulations identification and open the possibility to target specifically a specific subtype with the aims of either promoting beneficial classes or hampering deleterious ones.