Leptin treatment activates JAK2/STAT5 pathway and reverses the inhibition by Aβ42 of the JAK2/STAT5 activation. (a) Representative Western blot and (b) densitometric analyses show that treatment of organotypic slices with Aβ42 for 72 hours significantly decreases phosphorylation of JAK2 at Tyr1007/1008 residues. Leptin treatment increases basal levels and opposes Aβ42-induced decrease in p-Tyr1007/1008 JAK2 levels. (c,d) Treatment of organotypic slices with Aβ42 for 72 hours also decreases phosphorylation of STAT5 at Tyr694, potentially mitigating STAT5 activation. Leptin treatment increases basal levels of p-Tyr694 STAT5 and prevents the reduction in p-Tyr694 STAT5 induced by Aβ42. (e,f) Treatment of organotypic slices with Aβ42 reduces the translocation of p-Tyr694 STAT5 into the nucleus as evidenced by reduced levels of p-Tyr694 STAT5 in the nuclear fractions. Leptin treatment, alone or in the presence of Aβ42, increases the nuclear levels of p-Tyr694 STAT5. *p < 0.05, **p < 0.01 and ***p < 0.001 versus control; † p < 0.05 and † † p < 0.01 versus Aβ42.