TYK2 and Alzheimer disease: Very high concentrations of Aβ have been shown to increase tyrosine phosphorylation and transcriptional activity in a Tyk2 dependent manner in rodent models, and tyrosine phosphorylation of STAT3 is increased in AD brain [47], while inhibition of JAK-STAT3 signaling inhibits activation of astrocytes and microglia in animal models of neurodegeneration [48].