uptake of Aβ [141]. Interleukin-4, the prototypic M2 inducing cytokine, has been shown in several cases to mitigate Alzheimer’s disease pathology. Acute injection of 100 ng of IL-4 decreased Aβ levels in just a few days [32]. The Aβ decrease was correlated with an increase in pro Aβ phagocytic and degradation enzymes CD36 and neprilysin that colocalized to YM1 and Arg1+ M2 cells. Using an adeno-associated virus type 2 vector to provide sustained IL-4 expression, Kiyota et al. observed a reduction in gliosis, decreased Aβ, and improved spatial memory [100]. Interestingly, this same group attempted to replicate these results with IL-10 and only observed an increase in neurogenesis [101]. This discrepancy between M2-inducing cytokines suggests that different subtypes of alternatively activated microglia have unique functions. Interleukin-4-induced M2a microglia seem to be better in terms of engulfing Aβ, while IL-10-induced M2c microglia might play more of a supportive function.
