TI - Amyloid plaques develop in AAV-APP.SLA mice at 6 months p.i.with only marginal neuron loss . . AB - The impotency of AAV-APP.SLA in provoking neurodegeneration relative to AAV-Tau was not compensated for by time , as demonstrated in a fourth large series of experiments . We performed intracerebral injections in 4 cohorts of wild-type mice with AAV-APP.SLA or AAV-Tau.lt @@@@@ gt P301L , with AAV-EGFP as independent control next to the sham-injected group . All mice were analyzed for brain histology and immunohistochemistry at 6 months p.i. , which is the time-point studied so far . In AAV-Tau.lt @@@@@ gt P301L mice the pyramidal neurons were again lost completely in CA and also in deep cortical layers ( Figure 6A , in between red arrowheads in panel marked TauP301L ) . Conversely , in AAV-APP.SLA mice the CA regions were still largely intact at 6 months p.i. , very similar to AAV-EGFP injected and sham-operated mice . Nevertheless , typical amyloid plaques were evident in hippocampus and cortex of all AAV-APP.SLA injected mice at 6 months p.i. ( Figure 6B-D ) . This is much earlier than in APP.V717I mice and in bigenic biAT mice , which we attribute to the triple mutant APP.SLA in the current AAV model , which produces more Abeta42 than APP.V717I (Figure S2) expressed in our amyloid model [24] , [29] . As extra parameter for neurodegeneration , we measured the CA blade thickness in all AAV-injected mice of the four cohorts at 6 months p.i . . Relative to the nearly annihilated CA in AAV-Tau.lt @@@@@ gt P301L mice , these hippocampal region were hardly affected in AAV-APP.SLA mice ( Figure 7 ) . The combined data prove that mutant APP is only marginally potent and on a much longer time-scale , relative to protein Tau in provoking damage to pyramidal neurons , under very comparable experimental conditions . Moreover , IHC with AT180 demonstrated considerable tau-PHOSphorylation in the pyramidal neurons ( Figure 6G , H ) which tempts us to speculate that it is actually the beginning tauopathy that is detrimental to these neurons .