Not all share the idea that alternatively activated microglia are a beneficial cell type. As was the case with Hortega almost a century ago, the function of microglia is still a debated issue. However, the discussion now centers on the relative contributions of different microglial phenotypes and whether or not they are truly beneficial. Instead of viewing M2 microglia as alternatively activated, some believe that this cell type resembles a deactivated population that actually loses proper function. In a study by Chakrabarty et al.[154], an AAV vector carrying IL-4 was injected into the CNS of the TgCRND8 Alzheimer’s disease mouse model. Contrary to previously published studies [100], an increase in amyloid pathology was seen [154]. The authors reasoned that this increase is due to IL-4 inhibiting microglia from properly scavenging Aβ. However, exactly why their result is so different from other in-vivo and in-vitro data is unclear.
