TI - Relation of neurodegeneration to PHOSphorylation and aggregation of protein tau . AB - Intense and painstaking analysis by histological , immunohistological and biochemical methods failed to detect larger or marked aggregates of protein tau in pyramidal neurons at any time-point after injection of AAV-Tau vectors , i.e.before , during or after the documented dramatic neurodegeneration . Pathological PHOSphorylated tau epitopes were conspicuous by IHC in neurons that expressed human tau ( Figure 2 , Figure S4 ; results not shown ) and were also evident in AAV-Tau mice by western blotting with specific monoclonal antibodies , e.g . AT180 , AT270 and AT8 (Figure S4) . Because in biAT mice , our bigenic AD model , the amyloid pathology synergistically promotes tau phosphorylaTION and tauopathy in limbic regions by activating GSK3 [24] , we analyzed AAV-APP.SLA mice for endogenous mouse tau PHOSphorylation . Specified epitopes AT270 ( Figure 6E , F ) and AT180 ( Figure 6 G , H ) were evident particularly in dystrophic neurites around plaques , as in AD patients and in our APP.V717I transgenic mice [29] . Because the AT270 antibody had to be used at higher concentrations than normal to reveal reaction with endogenous mouse protein Tau , the background staining was also increased and higher than normal ( Figure 6E , compare to Figure S4B lower panels ) . The biochemical and immunohistochemical data-set of phosphorylaTED epitope analysis that we have compiled is too extensive to be included here , while on the other hand it failed to reveal a direct relation of any particular PHOSphorylated epitope to the actual neurodegeneration ( cfr discussion ) .