It remains unclear whether microglial function is detrimental or protective but insufficient during neurodegenerative diseases. In Cell, Amit and colleagues describe their use of massive parallel single-cell RNA-seq in a mouse model that expresses five Alzheimer's disease (AD)-associated mutations (5XFAD mice) to identify a distinct microglia subset present in AD, but not in healthy mice. These AD-associated microglia downregulate the expression of homeostatic genes (Cx3Cr1) and upregulate the expression of AD risk factors (Apoe, Trem2) and genes associated with lysosomal-phagocytic and lipid metabolism pathways as the disease progresses. These cells can be identified on the basis of the expression of CD9, CD11c, Clec7a and CD63, and are localized in the vicinity of b-amyloid plaques in 5XFAD mice and in brain samples from people with AD. Fully differentiated AD-associated microglia are absent in Trem2−/− mice, which have accelerated AD compared with wild-type mice on the 5XFAD background, thus suggesting that AD-associated microglia might be protective.

Cell (8 June 2017) http://dx.doi.org/10.1016/j.cell.2017.05.018