Open AccessTau‐Tubulin Kinase 1 Expression, Phosphorylation and Co‐Localization with Phospho‐ S er422 Tau in the A lzheimer's Disease Brain
Author(s) -
Lund Harald,
Cowburn Richard F.,
Gustafsson Elin,
Strömberg Kia,
Svensson Anne,
Dahllund Leif,
Malinowsky David,
Sunnemark Dan
Publication year - 2013
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12001
Subject(s) - hippocampal formation , neuropil , kinase , phosphorylation , immunohistochemistry , neurofibrillary tangle , biology , tangle , tau protein , senile plaques , population , microbiology and biotechnology , human brain , pin1 , neuroscience , pathology , chemistry , alzheimer's disease , biochemistry , medicine , central nervous system , disease , immunology , enzyme , environmental health , isomerase , pure mathematics , mathematics
Recent reports have implicated tau‐tubulin kinase 1 ( TTBK 1) in the pathological phosphorylation of tau that occurs in A lzheimer's disease ( AD ). The present study was undertaken to provide an extensive characterization of TTBK 1 m RNA and protein expression in human brain from AD cases and non‐demented controls so as to better understand the disease relevance of this novel kinase. I n situ hybridization and immunohistochemistry revealed abundant expression of TTBK 1 in the somatodendritic compartment of cortical and hippocampal neurons of both AD cases and controls. TTBK 1 immunoreactivity appeared to vary with the level of phospho‐tau staining, and was strong in the somatodendritic compartment of apparently healthy hippocampal neurons as well as in pre‐tangle neurons where it co‐localized with diffuse phospho‐ S er422 tau staining. Ser422 was confirmed as a TTBK 1 substrate in vitro , and an antibody towards the site, in addition to labeling AT8‐positive neurofibrillary tangles ( NFTs ), neuritic plaques and neuropil threads, also labeled a small population of neurons that were unlabeled with AT 8. These data suggest a role for TTBK 1 in pre‐tangle formation prior to the formation of fibrillar tau and strengthen the idea that tau is phosphorylated at S er422 at an early/intermediate stage in NFT formation.