Fig. 9

The JAK2-STAT3 pathway is a master regulator of astrocyte reactivity that contributes to AD deficits. SOCS3-mediated inhibition of this cascade in AD mouse models blocked and even reversed morphological and molecular hallmarks of reactivity. Conversely, activation of the JAK2-STAT3 pathway by viral gene transfer of JAK2ca in WT mice was sufficient to induce those hallmarks. Inhibition of this cascade in AD mice reduced amyloid deposition, deficits in spatial learning and synaptic dysfunction, showing that reactive astrocytes significantly contribute to AD pathological outcomes