Fig. 5

Tau-pT123 and tau-pT427 are targeted by TAOKs and are associated with tangles in AD and FTLD-tau brain. a In vitro kinase assays were carried out using GST-TAOK1 (1–314), GST-TAOK2 (1–314) and/or htau (2N4R) as indicated and samples immunoblotted with antibodies to detect tau-pS262/S356 (12E8), tau-pT427, tau-pT123 or total tau. b-c Entorhinal cortices from control (CTR), AD (Braak stage II-VI) or FTLD-tau brains were immunostained with antibodies to detect tau-pT123 (b) or tau-pT427 (c). Strong positive antibody immunoreactivity was observed for tau-pT123 and tau-pT427 at NFTs in each stage of AD and in FTLD-tau (arrows indicate magnified NFTs). d Sections from the entorhinal cortex of advanced AD (Braak stage VI) brains were immunostained with antibodies to detect tau-pS202/T205/S208 (AT8, green) or tau-pS262/S356 (12E8, green) and tau-pT123 or tau-pT427 (red) as indicated. Nuclei were counterstained with DAPI (blue). e AD (Braak VI) or control (CTR) hippocampal and entorhinal cortex brain samples were extracted with sarkosyl and low speed supernatants (LSS) or sarkosyl-soluble (SS) or sarkosyl-insoluble fractions (SI, insoluble tau) immunoblotted with antibodies to detect tau-pT123, tau-pT427 or total tau as indicated. Representative images and immunoblots are shown. Scale bar = 20 μm