TI - Neurotoxicity of AAV-Tau depends on the microtubule binding domain . AB - The hypothesis that microtubule binding of tau was involved in the observed neurodegeneration was supported by AAV-Tau255 that we generated to express C-terminally truncated Tau4R lacking the microtubule binding domain (Figure S5A) . At 3 weeks p.i . AAV-Tau255 was efficiently expressed at similar levels as full-length Tau in limbic and cortical regions (Figure S5A) . In contrast to full-length Tau , truncated Tau255 did not induce appreciable neurodegeneration , nor microgliosis ( Figure S5B , C ) . Interestingly , Tau255 appeared more localized to neuronal somata whereas full-length Tau distributed also to somatodendritic compartments of pyramidal neurons ( Figure S5D ) . Intriguingly , although Tau255 carried amino acid sequence 181-205 ( numbering of Tau441 ) , which upon phosphorylaTION constitutes the AT8 (pS202/pT205) and AT270 ( pT181 ) epitopes , these PHOSphorylated epitopes were hardly detectable in AAV-Tau255 injected mice ( Figure S5A ) . In contrast , PHOSphorylated epitope AT180 ( pT231 ) is located in the same region and equally evident in pyramidal neurons in AAV-Tau255 as in AAV-Tau.lt @@@@@ gt 4R and AAV-Tau.lt @@@@@ gt P301L mice ( Figure S5A ) .