Transcriptomic analysis of microglia from young and aged wild-type, NLRP3-/-, APP/PS1 and APP/PS1.NLRP3-/- mice.

Activation of the NLRP3 inflammasome has been implicated in the pathogenesis of Alzheimer's disease (AD), via the characterised release of IL-1ß and ASC specks. However, whether NLRP3 was involved in pathways beyond this remained unknown. Here were enriched CD11b+ cells from the brains of 4, 6 an 12 month old wild-type, NLRP3-/-, APP/PS1 and APP/PS1.NLRP3-/- mice for bulk RNA sequencing. We found that amyloid deposition was associated with an increase in the expression of genes encoding inflammatory or phagocytic proteins from 6 months onwards. Interestingly, loss of NLRP3 influences glutamine/glutamate-related metabolism and increases expression of microglial Slc1a3. The increase in Slc1a3 was observed in all mice on a NLRP3-/- background and at all ages examined, demonstrating a new role for this transporter in microglia. Overall design: Comparative gene expression analysis of RNA-seq for 4, 6 an 12 month oldwild-type, NLRP3-/-, APP/PS1 and APP/PS1.NLRP3-/- mice.