In addition to pharmacological methods to induce M2 activation, direct use of anti-inflammatory cytokines can lead to Aβ removal. As previously stated, the definitions for multiple phenotypes of alternatively activated macrophages originate from the periphery and therefore might not be completely applicable to the CNS. However, microglia treated with different anti-inflammatory cytokines exhibit unique activation states and functions. This topic is actively being pursued, in order to better understand differences between states [54]. For the sake of simplicity and a point of reference, we will refer to the activation states that are known for peripheral macrophages. TGFβ is a cytokine with potent anti-inflammatory properties that polarizes microglia to an M2c phenotype. Importantly, mice overexpressing TGFβ have reduced plaque loads [139] and mice deficient for TGFβ signaling showed elevated pathology [140]. In-vitro cultures also confirm that TGFβ treatment can enhance microglial 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
