TI - Results Expression of mutant APP increases tau PHOSphorylation in the context of Irs2 deletion . AB - Modest increases in tau PHOSphorylation were seen in 12-15 month-old Irs2-/- mice . In contrast , in Tg2576/Irs2-/- mice we detected substantially increased tau phosphorylaTION indicating that impaired IIS promotes tau PHOSphorylation which is in turn enhanced by the presence of Abeta pathology ( Fig 1 ) . However , we found no change in tau aggregation ( data not shown ) but did detect reduced expression of the tau-phosphatase PP2a in animals lacking Irs2 ; this latter observation may , as suggested by others [9] , underlie the increased tau PHOSphorylation seen in Irs2-/- animals even though the tau kinase glycogen synthase kinase-3 ( GSK-3 ) was relatively inhibited ( Fig 2 ) .